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

Background: 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.

periplasmic and membrane proteins are recognized by circulating and skin CD4+ T cells.

Background: Histologic and serologic studies suggest the induction of local and systemic ( )-specific CD4+ T cell responses to infection. We hypothesized that -specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment.

Methods: PBMC collected from 67 participants were screened by IFNγ ELISPOT response to sonicate.

Immunization with a tri-antigen syphilis vaccine significantly attenuates chancre development, reduces bacterial load, and inhibits dissemination of Treponema pallidum.

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.

B-Cell Epitope Mapping of TprC and TprD Variants of Subspecies Informs Vaccine Development for Human Treponematoses.

Several recent studies have focused on the identification, functional analysis, and structural characterization of outer membrane proteins (OMPs) of (). The species encompasses the highly related , , and subspecies of this pathogen, known to be the causative agents of syphilis, yaws, and bejel, respectively. These studies highlighted the importance of identifying surface-exposed OMP regions and the identification of B-cell epitopes that could be protective and used in vaccine development efforts.

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components.

SARS-CoV-2 provokes a robust T cell response. Peptide-based studies exclude antigen processing and presentation biology, which may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DCs to activate CD8 and CD4 T cells from convalescent people.

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components.

SARS-CoV-2 provokes a brisk T cell response. Peptide-based studies exclude antigen processing and presentation biology and may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DC to activate CD8 and CD4 T cells from convalescent persons.

Analytical Performance Characteristics of a New Transcription-Mediated Amplification Assay for Treponema pallidum.

This study evaluated the performance characteristics of a new research-use-only transcription-mediated amplification (TMA) assay for the detection of rRNA from Treponema pallidum. Analytical sensitivity determined using dark-field microscopy-quantitated T. pallidum was 1.

Streptococcus pyogenes Is Associated with Idiopathic Cutaneous Ulcers in Children on a Yaws-Endemic Island.

Exudative cutaneous ulcers (CU) in yaws-endemic areas are associated with subsp. (TP) and (HD), but one-third of CU cases are idiopathic (IU). Using mass drug administration (MDA) of azithromycin, a yaws eradication campaign on Lihir Island in Papua New Guinea reduced but failed to eradicate yaws; IU rates remained constant throughout the campaign.

Yaws re-emergence and bacterial drug resistance selection after mass administration of azithromycin: a genomic epidemiology investigation.

Background: In a longitudinal study assessing the WHO strategy for yaws eradication using mass azithromycin treatment, we observed resurgence of yaws cases with dominance of a single JG8 sequence type and emergence of azithromycin-resistant Treponema pallidum subspecies pertenue (T p pertenue). Here, we analyse genomic changes in the bacterial population using samples collected during the study.

Methods: We did whole bacterial genome sequencing directly on DNA extracted from 37 skin lesion swabs collected from patients on Lihir Island, Papua New Guinea, between April 1, 2013, and Nov 1, 2016.

Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men.

Syphilis rates in much of the world are now at their highest levels in almost three decades, and new approaches to controlling syphilis, including diagnostic tests with shorter window periods, are urgently needed. We compared the sensitivity of syphilis serological testing using the rapid plasma reagin (RPR) test with that of the combination of serological testing and an experimental 23S rRNA real-time transcription-mediated amplification (TMA) assay performed on rectal and pharyngeal mucosal swabs. PCR assays for the gene were performed on all TMA-positive specimens, as well as specimens from 20 randomly selected TMA-negative men.

Evaluation of the Protective Ability of the Treponema pallidum subsp. Tp0126 OmpW Homolog in the Rabbit Model of Syphilis.

analyses of subsp. genomes and predicted proteomes to search for homologs of known bacterial outer membrane proteins (OMPs) led to the identification of as a gene encoding a putative member of the OmpW family of porins/virulence factors. Our previous investigations on the role of Tp0126 in biology and syphilis pathogenesis showed that Tp0126 is fully conserved among strains and that transcription of is driven by σ These initial results pointed to a housekeeping function for this protein.

Treponema pallidum subsp. pallidum DNA and RNA in Semen of a Syphilis Patient Without Genital or Anal Lesions.

Treponema pallidum subsp. pallidum DNA and RNA were detected in a semen specimen of a syphilis patient with no genital or anal sores and no clinically evident orchitis. No nucleic acids were found in a urine sample of the same patient collected immediately before the semen sample.

Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates.

Background: Syphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens.

Topical treatment with gallium maltolate reduces Treponema pallidum subsp. pertenue burden in primary experimental lesions in a rabbit model of yaws.

Background: Gallium is a semi-metallic element known since the 1930s to have antimicrobial activity. This activity stems primarily from gallium's ability to mimic trivalent iron and disrupt specific Fe(III)-dependent pathways, particularly DNA synthesis (due to inhibition of ribonucleotide reductase). Because of its novel mechanism of action, gallium is currently being investigated as a new antibacterial agent, particularly in light of the increasing resistance of many pathogenic bacteria to existing antibiotics.

Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study.

Background: Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of yaws. We assessed the long-term efficacy of the WHO strategy for yaws eradication.

Development of a Multilocus Sequence Typing (MLST) scheme for Treponema pallidum subsp. pertenue: Application to yaws in Lihir Island, Papua New Guinea.

Background: Yaws is a neglected tropical disease, caused by Treponema pallidum subsp. pertenue. The disease causes chronic lesions, primarily in young children living in remote villages in tropical climates.

Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study.

Background: Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws.

Methods: This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre ≥1:8) latent or active yaws, between April, 2013, and May, 2015.

Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea.

Background: Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major causes of leg ulcers in children in Africa and the Pacific Region. We investigated the presence of DNA (PCR positivity) from these bacteria on asymptomatic people, flies, and household linens in an endemic setting.

Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains.

Background: High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T.

Isolation of Treponema DNA from Necrophagous Flies in a Natural Ecosystem.

Background: Recently, the World Health Organization launched a campaign to eradicate the tropical disease yaws, caused by the bacterium Treponema pallidum subsp. pertenue; however, for decades researchers have questioned whether flies act as a vector for the pathogen that could facilitate transmission.

Methods: A total of 207 fly specimens were trapped in areas of Africa in which T.

Molecular Typing of Treponema pallidum in Ocular Syphilis.

Background: Syphilis can have many clinical manifestations, including eye involvement, or "ocular syphilis." In 2015, an increase in reported cases of ocular syphilis and potential case clusters raised concern for an oculotropic strain of Treponema pallidum, the infectious agent of syphilis. Molecular typing was used to examine strains found in cases of ocular syphilis in the United States.

Syphilis? An Unusual Cause of Surgical Emergency in a Human Immunodeficiency Virus-Infected Man.

We report on a human immunodeficiency virus-infected man undergoing urgent anorectal surgery, with multi-centimeter fungating masses discovered inside the anus. Initial pathology was inconclusive. After the patient developed a disseminated rash postoperatively determined to be secondary syphilis, the anorectal pathology was reviewed and Treponema pallidum DNA was amplified by polymerase chain reaction from the mass.

Mass treatment with single-dose azithromycin for yaws.

Background: Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan.

Methods: We performed repeated clinical surveys for active yaws, serologic surveys for latent yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which yaws was endemic.

Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study.

Background: Skin infections with ulceration are a major health problem in countries of the south Pacific region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacific islands-Haemophilus ducreyi-as causes of skin ulceration in a yaws-endemic region.

Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains.

Background: The pathogenic non-cultivable treponemes include three subspecies of Treponema pallidum (pallidum, pertenue, endemicum), T. carateum, T. paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme (Simian isolate).