Methods.Treponema pallidum DNA was isolated from 158 patients with syphilis the United States, China, Ireland, and Madagascar 15 T. isolates. Six typing targets were assessed: (1) number of 60- bp repeats in acidic repeat protein gene, (2) restriction fragment length polymorphism (RFLP) analysis (tpr) subfamily II genes, (3) RFLP tprC (4) determination tprD allele gene locus, (5) presence a 51-bp insertion between tp0126 tp0127, (6) sequence an 84-bp region tp0548. The combination 1 2...

Success of neurosyphilis treatment is defined by normalization cerebrospinal fluid (CSF) and clinical abnormalities. The goal this study was to determine whether serum rapid plasma reagin (RPR) titer could accurately predict success.One hundred ten patients who were enrolled in a longitudinal CSF abnormalities syphilis had asymptomatic syphilitic meningitis, symptomatic or eye disease treated for neurosyphilis. At 4, 7, 13 months after treatment, RPR analyzed normalization. Odds ratios each...

Asymptomatic neurosyphilis is more difficult to diagnose in human immunodeficiency virus (HIV)-infected patients because HIV itself can cause cerebrospinal fluid (CSF) pleocytosis. The proportion of CSF lymphocytes that are B cells elevated neurosyphilis, suggesting the concentration cell chemoattractant, chemokine (C-X-C motif) ligand 13 (CXCL13) may also be elevated.CSF and blood were collected from 199 HIV-infected with syphilis neurosyphilis. Serum CXCL13 concentrations...

Abstract Syphilis is a sexually transmitted infection caused by Treponema pallidum subspecies and may lead to severe complications. Recent years have seen striking increases in syphilis many countries. Previous analyses suggested one lineage of syphilis, SS14, expanded recently, indicating emergence single pandemic azithromycin-resistant cluster. Here we use direct sequencing T. combined with phylogenomic show that both SS14- Nichols-lineages are simultaneously circulating clinically...

BackgroundThe increasing incidence of syphilis and the limitations first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, pregnancy, highlight need to expand therapeutic repertoire for effective management this disease. We assessed in-vitro efficacy 18 antibiotics from several classes on Treponema pallidum subspecies (T pallidum), bacteria.MethodsUsing culture system T pallidum, we exposed pathogen a concentration range each tested antibiotic. After 7-day...

To identify factors that affect normalization of laboratory measures after treatment for neurosyphilis, 59 subjects with neurosyphilis underwent repeated lumbar punctures and venipunctures completion therapy. The median duration follow-up was 6.9 months. Stepwise Cox regression models were used to determine the influence clinical features on cerebrospinal fluid (CSF), white blood cells (WBCs), CSF protein concentration, Venereal Disease Research Laboratory (VDRL) reactivity, serum rapid...

Pathogens that cause chronic infections often employ antigenic variation to evade the immune response and persist in host. In Treponema pallidum (T. pallidum), causative agent of syphilis, TprK Ag undergoes seven V regions (V1-V7) by nonreciprocal recombination silent donor cassettes with tprK expression site. These are targets host humoral during experimental infection. The present study addresses causal role acquired selection variants two ways: 1) investigating arising immunocompetent...

The cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test is a mainstay for neurosyphilis diagnosis, but it lacks diagnostic sensitivity and logistically complicated. rapid plasma reagin (RPR) easier to perform, its appropriateness use on CSF controversial.RPR reactivity was determined from 149 individuals with syphilis using 2 methods. CSF-RPR performed according the method serum. CSF-RPR-V recommended CSF-VDRL. Laboratory-defined included reactive CSF-fluorescent...

ABSTRACT Limited data suggest that the cerebrospinal fluid Treponema pallidum particle agglutination assay (CSF-TPPA) is sensitive and a CSF hemagglutination (CSF-TPHA) titer of ≥1:640 specific for neurosyphilis diagnosis. CSF-TPPA reactivity were determined convenience sample 191 samples from individuals enrolled in study abnormalities syphilis (training set). The sensitivity reactive test specificity at serial higher dilutions determined. Subsequently, 1:640 dilution was all available...

Although azithromycin promised to be a safe and effective single-dose oral treatment of early syphilis, failure has been documented is associated with mutations in the 23S rDNA corresponding Treponema pallidum strains. The prevalence strains harboring these varies throughout United States world. We examined T. circulating Seattle, Washington, from 2001 2010 determine 2 macrolide resistance whether were certain strain types.Subjects enrolled separate ongoing study cerebrospinal fluid...

Despite more than a century of research, genetic manipulation Treponema pallidum subsp. ( T . ), the causative agent syphilis, has not been successful. The lack engineering tools severely limited understanding mechanisms behind success as pathogen. A recently described method for in vitro cultivation , however, made it possible to experiment with transformation and selection protocols this Here, we describe an approach that successfully replaced tprA tp0009 ) pseudogene SS14 strain kanamycin...

Background The TprK protein of the syphilis agent, Treponema pallidum subsp. ( T . ), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire 53 silent chromosomal donor cassettes (DCs) into single tprK expression site to continually generate variants. Several lines research developed over last two decades support theory that this mechanism is central ’s ability for...

To determine whether the 23S rRNA mutation that confers macrolide resistance is present in >1 Treponema pallidum strain, 58 isolates collected between 2001 and 2005 were screened for this an unrelated sequence distinguishes strains. The odds of identifying a macrolide-resistant strain increased over time (P=.006). In subjects who had received macrolides previous year, relative risk harboring resistant was 2.2 (95% confidence interval, 1.1-4.4; P=.02). strains not identical. These findings...

The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. (T. pallidum) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance controlled studies assess differential treponemal gene expression, generation loss-of-function mutants evaluate contribution specific genetic loci T. virulence. Building on this progress, we engineered SS14 strain express a red-shifted green fluorescent protein...

Abstract Background Syphilis cases continue to increase rapidly in the US. Molecular detection of pathogen, Treponema pallidum (TP) may speed turnaround time (TAT) and resolve ambiguous results from current diagnostics methods, which require stepwise serologic testing. Here we describe validation clinical performance a loop-mediated isothermal amplification (LAMP) assay for TP. Methods Candidate LAMP primers targeting 23S rRNA locus TP were evaluated best performing set was used per Clinical...

Background. The relationship between neuroinvasion and other manifestations of syphilis the infecting strain Treponema pallidum is not known.

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 oculotropic strain Treponema pallidum , the infectious agent syphilis. Molecular typing was used to examine strains found United States. Methods after a advisory issued by Centers Disease Control Prevention, pretreatment specimens from US patients with were sent research laboratory...

Background. Human immunodeficiency virus (HIV)–infected individuals may have poorer serological responses to syphilis treatment and be more likely experience neurosyphilis. Treponema pallidum is cleared from sites of infection by opsonization, ingestion, killing macrophages. Methods. Serum samples 235 with were tested for T. pallidum–specific opsonic activity. Blood concentrations determined real-time polymerase chain reaction amplification the tp0574 gene, was detected in cerebrospinal...

Current guidelines recommend lumbar puncture (LP) in patients with syphilis who have neurologic symptoms.A total of 81 human immunodeficiency virus (HIV)-uninfected individuals and 385 HIV-infected enrolled a study cerebrospinal fluid (CSF) abnormalities underwent LP structured symptom history, including assessment headache; stiff neck; photophobia; ocular inflammation; vision, hearing, or sensory loss; gait incoordination. Neurosyphilis was defined as reactive CSF-Venereal Disease Research...

Abstract Background The influence of previous syphilis on the course a subsequent episode is unknown. Methods Individuals enrolled in study cerebrospinal fluid (CSF) abnormalities were allowed to enroll again with syphilis. For each participant, index was defined as most recent for which entry visit performed within 30 days diagnosis date. Venipuncture and lumbar puncture (LP) performed. Total number episodes determined by review medical public health records. T. pallidum DNA blood rRNA CSF...

<h3>Abstract</h3> Determining how and often asexual lineages emerge within sexual species is central to our understanding of sex-asex transitions the long-term maintenance sex. Asexuality can arise "by transmission" from an existing lineage a new one, through different types crosses. The occurrence these crosses, cryptic sex, variation in ploidy recombination asexuals greatly complicates study transitions, as they preclude use standard phylogenetic methods genetic distance metrics. In this...

Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling response to spirochetal lipoproteins. We investigated whether common SNPs TLR1, TLR2, or TLR6 were associated with laboratory- clinically-defined neurosyphilis.

High rates of 23S rDNA mutations implicated in macrolide resistance have been identified Treponema pallidum samples from syphilis patients many countries. Nonetheless, some clinicians reluctant to abandon azithromycin as a treatment for syphilis, citing the lack causal association between these and clinical evidence drug resistance. Although has demonstrated vivo historical Street 14 strain, no recent T. isolates tested. We used well-established rabbit model determine efficacy against mutant...

Developing a vaccine against Treponema pallidum subspecies pallidum, the causative agent of syphilis, remains public health priority. Syphilis design efforts have been complicated by lack an in vitro T. culture system, prolific antigenic variation outer membrane protein TprK, and functional annotation for nearly half genes. Understanding genetic basis reinfection can provide insights into among strains that escape cross-protective immunity. Here, we present comparative genomic sequencing...

Abstract Background Data comparing neurosyphilis treatment regimens are limited. Methods Participants were enrolled in a study of cerebrospinal fluid (CSF) abnormalities syphilis that was conducted at the University Washington between April 2003 to May 2014. They diagnosed with and referred by their providers due concerns for neurosyphilis. We evaluated 150 people CSF who treated either intravenous aqueous penicillin G (PenG) or intramuscular procaine plus oral probenecid (APPG-P). An...