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.

Correlation between hospital rating agencies' data: An analysis and recommendation.

Hospital rating agencies exist to inform consumers through publicly available patient safety data. The large number of rating agencies, the variability in their methodologies and data presentations leave few consumers considering these data in making healthcare decisions. The objective of this study was to analyze the comparability of data from four different healthcare rating agencies to understand whether there exists a correlation among the rating agencies' published data. Four well-known rating agencies' data were gathered for 30 Connecticut hospitals and analyzed using correlation methods. The overall rating score was used for comparison accounting for patients' probability of referencing this score in determining a hospital's safety. The results indicate little or no correlation between ratings of Connecticut hospitals among the reviewed rating agencies. The only statistically significant correlation was between CMS and Leapfrog. The lack of correlation among rating agencies' publicly available data identified in this study leads to consumer confusion. This research provides support for the need for a valid, reliable, and transparent healthcare rating system to inform patient decision making. These findings can be used to advocate for a legislatively mandated national reporting system that focuses on user understanding of the data.

Long-term effect of low frequency stimulation of STN on dysphagia, freezing of gait and other motor symptoms in PD.

OBJECTIVE: To evaluate the long-term effect of 60 Hz stimulation of the subthalamic nucleus (STN) on dysphagia, freezing of gait (FOG) and other motor symptoms in patients with Parkinson's disease (PD) who have FOG at the usual 130 Hz stimulation. METHODS: This is a prospective, sequence randomised, crossover, double-blind study. PD patients with medication refractory FOG at 130 Hz stimulation of the STN were randomised to the sequences of 130 Hz, 60 Hz or deep brain stimulation off to assess swallowing function (videofluoroscopic evaluation and swallowing questionnaire), FOG severity (stand-walk-sit test and FOG questionnaire) and motor function (Unified PD Rating Scale, Part III motor examination (UPDRS-III)) at initial visit (V1) and follow-up visit (V2, after being on 60 Hz stimulation for an average of 14.5 months), in their usual medications on state. The frequency of aspiration events, perceived swallowing difficulty and FOG severity at 60 Hz compared with 130 Hz stimulation at V2, and their corresponding changes at V2 compared with V1 at 60 Hz were set as primary outcomes, with similar comparisons in UPDRS-III and its subscores as secondary outcomes. RESULTS: All 11 enrolled participants completed V1 and 10 completed V2. We found the benefits of 60 Hz stimulation compared with 130 Hz in reducing aspiration frequency, perceived swallowing difficulty, FOG severity, bradykinesia and overall axial and motor symptoms at V1 and persistent benefits on all of them except dysphagia at V2, with overall decreasing efficacy when comparing V2 to V1. CONCLUSIONS: The 60 Hz stimulation, when compared with 130 Hz, has long-term benefits on reducing FOG, bradykinesia and overall axial and motor symptoms except dysphagia, although the overall benefits decrease with long-term use. CLINICAL TRIAL REGISTRATION: NCT02549859; Pre-results.

Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD.

OBJECTIVES: To study whether 60-Hz stimulation, compared with routine 130 Hz, improves swallowing function and freezing of gait (FOG) in patients with Parkinson disease (PD) who undergo bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). METHODS: We studied 7 patients with PD who experienced FOG that persisted despite routine 130-Hz stimulation and dopaminergic medication. Each patient received 3 modified barium swallow (MBS) studies in a single day under 3 DBS conditions in the medication-on state: 130 Hz, 60 Hz, or DBS off, in a randomized double-blind manner. The laryngeal penetration and aspiration events were cautiously assessed, and a swallowing questionnaire was completed. The Unified Parkinson's Disease Rating Scale, Part III motor score, axial subscore, tremor subscore, and FOG by a questionnaire and stand-walk-sit test were also assessed. The best DBS condition (60 Hz here) producing the least FOG was maintained for 3 to 8 weeks, and patients were assessed again. Changes in measurements between the 60 Hz and 130 Hz were analyzed using paired t test, with swallowing function as primary and the remainder as secondary outcomes. Changes between other DBS conditions were further explored with Bonferroni correction. RESULTS: Compared with the routine 130 Hz, 60-Hz stimulation significantly reduced aspiration frequency by 57% on MBS study and perceived swallowing difficulty by 80% on questionnaire. It also significantly reduced FOG, and axial and parkinsonian symptoms. The benefits at 60-Hz stimulation persisted over the average 6-week assessment. CONCLUSIONS: Compared with the routine 130 Hz, the 60-Hz stimulation significantly improved swallowing function, FOG, and axial and parkinsonian symptoms in patients with PD treated with bilateral STN-DBS, which persisted over the 6-week study period. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with PD who experience FOG, STN-DBS at 60 Hz decreases aspiration events observed during MBS compared with DBS at 130 Hz.