Syphilis testing in blood donors, France, 2007 to 2022.

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

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Treponema pallidum protein Tp0136 promotes angiogenesis to facilitate the dissemination of Treponema pallidum.

The incompletely eliminated Treponema pallidum (T. pallidum) during primary syphilis chancre infection can result in the progression of secondary, tertiary, or latent syphilis in individuals, suggesting that T. pallidum has successfully evaded the immune response and spread to distant sites. The mechanism underlying the dissemination of T. pallidum is unclear. Here, a syphilitic rabbit model dorsal-injected with recombinant Tp0136 protein or Tp0136 antibody subcutaneously was used to demonstrate the role of Tp0136 protein in promoting the dissemination of T. pallidum to the testis and angiogenesis in vivo; vascular endothelial cell line HMEC-1 was employed to display that Tp0136 protein enhances the angiogenesis. Furthermore, the three-dimensional microfluidic angiogenesis system showed that the angiogenesis would heighten vascular permeability. Then transcriptome sequencing analysis, in conjunction with cell-level validation, elucidated the critical role of the PI3K-AKT signaling pathway in the promotion of angiogenesis by Tp0136 protein, resulting in heightened permeability. These findings elucidate the strategy employed by T. pallidum in evading immune clearance.

Improved efficiency using sequential automated immunoassays for syphilis screening in blood donors.

Using sequential immunoassays for the screening of blood donors is well described for viral serology testing but not for the screening of syphilis. In this study, we report the evaluation results and 2-year sequential testing data using two highly sensitive automated serology assays, the Alinity s Syphilis chemiluminescent immunoassay for screening, with all repeatedly reactive samples then tested on the Elecsys Syphilis electrochemiluminescence immunoassay. We screened 1,767,782 blood donor samples between 7 July 2021 and 6 July 2023 and found the Alinity false-positive rate to be low at 0.08% (1,456/1,767,782). The common false-positive rate between the two assays was also low (3.83%, 58/1,514). Concordantly reactive samples were further tested using a Treponema pallidum particle agglutination test, a rapid plasma reagin test, and a fluorescent treponemal antibody absorption test. There were 262/1,376 concordantly reactive Alinity and Elecsys blood donor samples with reactivity on one or more of the confirmatory tests. A total of 26/1,376 donors had a current syphilis infection, 152/1,376 reported a past history of syphilis and had been treated, and 84/1,376 did not report a past history of syphilis. We suggest that future studies could explore the use of sequential immunoassays to aid in the serodiagnosis for syphilis. IMPORTANCE: The serodiagnosis for syphilis usually follows two methodologies-a "traditional" algorithm using a non-treponemal test followed by confirmation using a treponemal test, or a "reverse" algorithm using a treponemal test followed by a non-treponemal test. There are limited reports in the literature of using a modified reverse algorithm (treponemal test followed by a second treponemal test), and to the best of knowledge, there are currently no published articles using two highly sensitive automated immunoassays to aid the serodiagnosis of syphilis. In addition, the Treponema pallidum particle agglutination (TPPA) assay is commonly used as a confirmatory test for the diagnosis of syphilis. With the withdrawal of the TPPA assay from Australia and presumably from the global market also, alternative testing algorithms are now required. This study provides proof of concept for using sequential immunoassays in the diagnosis of syphilis.

A novel syphilis Treponema pallidum lipoprotein peptide antigen diagnostic assay using red cell kodecytes in routine blood centre column agglutination testing platforms.

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

Majority of Treponema pallidum ssp. pallidum MLST allelic profiles in the Czech Republic (2004-2022) belong to two SS14-like clusters.

Syphilis is a multistage sexually transmitted disease caused by Treponema pallidum ssp. pallidum. In the Czech Republic, there are around 700-800 new syphilis cases annually, continuously increasing since 2012. This study analyzed a total of 1228 samples from 2004 to 2022. Of the PCR-positive typeable samples (n = 415), 68.7% were fully-typed (FT), and 31.3% were partially-typed. Most of the identified isolates belonged to the SS14-clade and only 6.3% were the Nichols-like cluster. While in the beginning of sample collection isolates have been macrolide-susceptible, recent isolates are completely resistant to macrolides. Among the FT samples, 34 different allelic profiles (APs) were found. Most of the profiles (n = 27) appeared just once in the Czech population, while seven profiles were detected more than twice. The most frequent APs belonged to two separate groups of SS14-like isolates, including group of 1.3.1 (ST 1) and 1.26.1 (ST 25) profiles, and the second group containing 1.1.8 (ST 3), 1.1.1 (ST 2), and 1.1.3 (ST 11) (representing 57.5%, and 25.3% of all detected APs, respectively). Both groups consistently differed in 6 nucleotide positions in five genes (TP0150, TP0324, TP0515, TP0548, and TP0691) coding amino-acid replacements suggesting that one or more of these differences could be involved in the higher success of the first group.

Seroinfection of Antibodies to Toxoplasma gondii, Parvovirus B19, Treponema pallidum, and HIV in a Pregnant Attending a Medical Center in Northern Peru.

Introduction: Transplacental infections are frequent, especially in developing countries, where limited screening is performed to find infectious agents in the pregnant population. We aim to determine the clinical and epidemiological characteristics and seroinfection of antibodies against Toxoplasma, parvovirus B19, T. pallidum, and HIV in pregnant women who attended the Motupe Health Center in Lambayeque, Peru during July-August 2018. Methods: A descriptive cross-sectional study was conducted in 179 pregnant women interviewed with a standardized questionnaire. ELISA was used to determine antibodies to Toxoplasma and parvovirus B19. The detection of syphilis and HIV was conducted using immunochromatography, while the detection of hepatitis B was conducted using FTA-ABS and immunofluorescence, respectively. Results: Of 179 pregnant women, syphilis and HIV infections routinely included in the screening of pregnant women presented a seroinfection of 2.2 and 0.6%, respectively. Toxoplasmosis seroinfection was 25.1%, while IgM antiparvovirus B19 was 40.8%, revealing that pregnant women had an active infection at the time of study. Conclusion: The level of seroinfection of toxoplasmosis reveals the risk to which pregnant women who participated in the study are exposed. The high seroinfection of parvovirus B19 could explain the cases of spontaneous abortion and levels of anemia in newborn that have been reported in Motupe, Lambayeque, Peru. However, future causality studies are necessary to determine the significance of these findings.

A Novel Treponema pallidum Subspecies pallidum Strain Associated With a Painful Oral Lesion Is a Member of a Potentially Emerging Nichols-Related Subgroup.

BACKGROUND: Early syphilitic lesions are typically painless; however, several recent case studies have included patients with tender lesions and no evidence of concurrent infections. Here we present the manifestations and serological and molecular findings of a patient from New York State with a painful tongue lesion. METHODS: The diagnosis of syphilis was based on a combination of physical examination, serologic, pathologic, and immunohistochemical findings. DNA obtained from a formalin-fixed, paraffin-embedded biopsy was used to characterize the infecting pathogen using polymerase chain reaction, multilocus sequence typing, and whole-genome sequencing methods. RESULTS: Polymerase chain reaction and multilocus sequence typing of the biopsy specimen confirmed infection with T. pallidum subspecies pallidum ( T. pallidum ) of the Nichols cluster. Whole-genome sequencing analysis of this strain (herein called NYMC01) showed that it contained 17 unique single nucleotide variations and 4 more complex genetic differences; this novel genotype matched only 2 specimens, both from a patient in Seattle, Washington. The presence of this rare genotype in 2 geographically distinct locations suggests the potential emergence and spread of a new subgroup of the Nichols cluster. CONCLUSIONS: To our knowledge, this is the first genomic sequence obtained from a T. pallidum strain linked to a painful lesion, and the third description of whole-genome sequencing of T. pallidum from formalin-fixed, paraffin-embedded tissue. Analysis of additional specimens may reveal that the NYMC01-related genotype represents an emerging T. pallidum subgroup and may also aid in determining whether the painful clinical presentation of primary syphilis is related to specific T. pallidum genotypes.

"Syphilitic Hepatitis": A Comprehensive Review of Clinical Features, Diagnostic Approaches, and Management Considerations.

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

Analysis of molecular subtypes and antibiotic resistance in Treponema pallidum isolates from blood donors in Khyber Pakhtunkhwa, Pakistan.

Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.

Ocular vs neurosyphilis. are they the same? A guide to investigation and management.

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

A case for implementing an HSV1/2, VZV, and syphilis lesion panel in Manitoba, Canada.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis.

Two-Stage Syphilis Testing.

A 54-year-old woman presented with erythematous annular and indurated plaques on her face, trunk, and extremities and had false-positive syphilis test results during 2 pregnancies 25 and 22 years prior. What would you do next?

Syphilis Has Surged for Reasons That Go Beyond the Pathogen That Causes It.

This Medical News story discusses the multiple factors contributing to the resurgence of syphilis in the US.