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.

Physicians' Perspectives on HL7 Information Policy Sensitive Value Set: A Validation Study through Health Concept Categorization.

The Health Level 7 (HL7) organization introduced the Information Sensitivity Policy Value Set with 45 sensitive data categories to facilitate the implementation of granular electronic consent technology. The goal is to allow patients to have control over the sharing of their sensitive medical records. This study represents the first attempt to explore physicians' viewpoints on these categories. Twelve physicians participated in a survey, leading to revisions in 21 HL7 categories. They later classified 600 clinical data items through a second survey using the updated categories. Participants' perspectives were documented, and data analysis included descriptive measures and heat maps. In the first survey, six participants suggested adding 19 new categories (e.g., personality disorder), and modifying 25 category definitions. Two new categories and sixteen revised category definitions were incorporated to support more patient-friendly content and inclusive language. Fifteen new category recommendations were addressed through a revision of category definitions (e.g., personality disorder described as a behavioral health condition). In the second survey, data categorizations led to recommendations for more categories from ten participants. Future revisions of the HL7 categories should incorporate physicians' viewpoints, validate the categories using patient data or/and include patients' perspectives, and develop patient-centric category specifications.

Errores innatos de la inmunidad en adultos / Inborn errors of immunity in adults

Introducción: La inmunodeficiencia común variable es un error innato de la inmunidad que tiene su pico de incidencia en la edad adulta. Se caracteriza por una susceptibilidad aumentada a padecer infecciones respiratorias, autoinmunidad y malignidad, secundario a un estado de hipogammaglobulinemia e inmunodisregulación, causado por mutaciones e interacciones genéticas parcialmente comprendidas. El diagnóstico es de exclusión, tiene una gran heterogeneidad clínica y comúnmente es diagnosticado de forma errónea. Objetivo: Describir un caso clínico de un paciente afectado por un error innato de la inmunidad. Caso clínico: Hombre de 35 años que se presenta a la consulta de Medicina Interna - Inmunología refiriendo un cuadro clínico de 3 años de evolución consistente en múltiples episodios de infecciones sino-pulmonares en los últimos meses, presentaba tos productiva, dificultad respiratoria y pérdida de peso no intencional de aproximadamente 8 kg. Conclusiones: La inmunodeficiencia común variable debe considerarse dentro de los diagnósticos diferenciales en todo paciente que presente alguna de sus manifestaciones clínicas, principalmente aquellas relacionadas con infecciones respiratorias a repetición, antecedente que el paciente puede presentar como relevante en sus consultas de primer nivel con medicina general o con especialistas. Su aproximación diagnóstica consiste en la solicitud de niveles séricos de inmunoglobulinas, prueba de laboratorio de fácil acceso para cualquier clínico independiente de su nivel de atención y su tratamiento se fundamenta en la administración periódica de inmunoglobulina humana exógena de forma endovenosa o subcutánea(AU)

Introduction: Common variable immunodeficiency is an inborn error of immunity that has its peak incidence in adulthood. It is characterized by an increased susceptibility to respiratory infections, autoimmunity and malignancy, secondary to a state of hypogammaglobulinemia and immunodysregulation, caused by mutations and partially understood genetic interactions. The diagnosis is one of exclusion, has great clinical heterogeneity and is commonly misinterpreted. Objective: To describe a clinical case of a patient affected by an inborn error of immunity. Methods: Retrospective description of a case report. Conclusions: Common variable immunodeficiency disorder should be considered within the differential diagnoses in every patient who presents any of its clinical manifestations, mainly those related to recurrent respiratory infections, an antecedent that the patient may present as relevant during the first-level consultations with general medicine physicians or with specialists. Its diagnostic approach consists in measuring serum immunoglobulin levels, an easily accessible laboratory test for any clinic physician regardless of their healthcare level, while its treatment is based on the periodic administration of exogenous human immunoglobulin intravenously or subcutaneously(AU)

Síndrome de cáncer hereditario de mama y ovario: aplicación clínica / Hereditary breast and ovarian cancer syndrome: Clinical application

Aportar al ginecólogo herramientas para la identificación de pacientes con riesgo de síndrome de cáncer hereditario de mama y ovario (SCHMO), y brindar consejería en el manejo preventivo de pacientes con este síndrome.Materiales y métodos: a partir de un caso hipotético se formulan preguntas relacionadas con el riesgo de desarrollar cáncer de mama y ovario en pacientes con SCHMO. Para responder estas preguntas se realizó una revisión de la literatura pertinente en las bases de datos Medline vía PubMed, ScienceDirect y SciELO. Se utilizaron los términos MESH "Síndrome de cáncer de mama y ovario hereditario", "Neoplasias ováricas", "Neoplasias de la mama", "Genes BRCA1", "Genes BRCA2" y su equivalente en inglés. Los resultados se restringieron a artículos publicados entre el 2005 y 2015.Resultados: a través de la búsqueda en PubMed se obtuvieron 56 artículos, de los cuales se seleccionaron 45. En ScienceDirect y SciELO se encontraron 7 artículos. Además, se incluyeron 4 artículos de fuentes no ligadas a estas bases de datos.Conclusiones: el ginecoobstetra debe identificar pacientes con riesgo de presentar el síndrome de cáncer hereditario de mama y ovario, y explicar a los pacientes la importancia de la realización de las pruebas moleculares de los genes BRCA1 y BRCA2 y de participar en equipos multidisciplinarios que además deben incluir al genetista, cirujano, los oncólogos y al paciente para la toma de decisiones médicas de acuerdo con los resultados moleculares...

To provide gynaecologists with tools for the identification of patients at risk of hereditary breast and ovarian cancer syndrome (HBOC) and present advise regarding the preventive management of patients with this syndrome.Materials and methods: Questions were asked in relation to the risk of patients with HBOC developing breast and ovarian cancer. To answer those questions, a review of the relevant literature was conducted in the Medline database via PubMed, and in ScienceDirect and SciELO. The MESH terms used were Breast and Ovarian Cancer Syndrome, Ovarian Neoplasms, Breast Neoplasms, BRCA1 Genes, BRCA2 Genes, and their equivalent in English. Results were limited to articles published between 2005 and 2015.Results: Overall, 56 articles were found in PubMed, of which 45 were selected. The search in ScienceDirect and SciELO resulted in 7 articles. Additionally, 4 articles from other sources not linked to these data bases were also included.Conclusions: Obstetric gynaecologists must identify patients at risk of presenting Hereditary Breast and Ovarian Cancer Syndrome, and explain to the patients the importance of performing molecular testing for BRCA1 and BRCA2 genes; and they must participate in multi-disciplinary teams consisting also of geneticists, surgeons, oncologists and patients for medical decision-making in accordance with the molecular results...