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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.
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Sífilis , Treponema pallidum , Humanos , Treponema pallidum/genética , Treponema pallidum/inmunología , Treponema pallidum/aislamiento & purificación , Colombia/epidemiología , Sífilis/epidemiología , Sífilis/microbiología , Estudios Transversales , Masculino , Adulto , Femenino , Vacunas Bacterianas/inmunología , Variación Genética , Desarrollo de Vacunas , Adulto Joven , Persona de Mediana Edad , Secuenciación Completa del Genoma , AnimalesRESUMEN
Shiga toxin-producing Escherichia coli (STEC) poses a significant public health risk due to its zoonotic potential and association with severe human diseases, such as hemorrhagic colitis and hemolytic uremic syndrome. Ruminants are recognized as primary reservoirs for STEC, but swine also contribute to the epidemiology of this pathogen, highlighting the need for effective prevention strategies across species. Notably, a subgroup of STEC that produces Shiga toxin type 2e (Stx2e) causes edema disease (ED) in newborn piglets, economically affecting pig production. This study evaluates the immunogenicity of a chimeric protein-based vaccine candidate against STEC in pregnant sows and the subsequent transfer of immunity to their offspring. This vaccine candidate, which includes chimeric proteins displaying selected epitopes from the proteins Cah, OmpT, and Hes, was previously proven to be immunogenic in pregnant cows. Our analysis revealed a broad diversity of STEC serotypes within swine populations, with the cah and ompT genes being prevalent, validating them as suitable antigens for vaccine development. Although the hes gene was detected less frequently, the presence of at least one of these three genes in a significant proportion of STEC suggests the potential of this vaccine to target a wide range of strains. The vaccination of pregnant sows led to an increase in specific IgG and IgA antibodies against the chimeric proteins, indicating successful immunization. Additionally, our results demonstrated the effective passive transfer of maternal antibodies to piglets, providing them with immediate, albeit temporary, humoral immunity against STEC. These humoral responses demonstrate the immunogenicity of the vaccine candidate and are preliminary indicators of its potential efficacy. However, further research is needed to conclusively evaluate its impact on STEC colonization and shedding. This study highlights the potential of maternal vaccination to protect piglets from ED and contributes to the development of vaccination strategies to reduce the prevalence of STEC in various animal reservoirs.
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Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen that causes gastroenteritis and Hemolytic Uremic Syndrome. Cattle are the main animal reservoir, excreting the bacteria in their feces and contaminating the environment. In addition, meat can be contaminated by releasing the intestinal content during slaughtering. Here, we evaluated the safety and immunogenicity of a vaccine candidate against STEC that was formulated with two chimeric proteins (Chi1 and Chi2), which contain epitopes of the OmpT, Cah and Hes proteins. Thirty pregnant cows in their third trimester of gestation were included and distributed into six groups (n = 5 per group): four groups were administered intramuscularly with three doses of the formulation containing 40 µg or 100 µg of each protein plus the Quil-A or Montanide™ Gel adjuvants, while two control groups were administered with placebos. No local or systemic adverse effects were observed during the study, and hematological parameters and values of blood biochemical indicators were similar among all groups. Furthermore, all vaccine formulations triggered systemic anti-Chi1/Chi2 IgG antibody levels that were significantly higher than the control groups. However, specific IgA levels were generally low and without significant differences among groups. Notably, anti-Chi1/Chi2 IgG antibody levels in the serum of newborn calves fed with colostrum from their immunized dams were significantly higher compared to newborn calves fed with colostrum from control cows, suggesting a passive immunization through colostrum. These results demonstrate that this vaccine is safe and immunogenic when applied to pregnant cows during the third trimester of gestation.
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Infecciones por Escherichia coli , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Vacunas de Subunidad , Animales , Bovinos , Femenino , Embarazo , Infecciones por Escherichia coli/prevención & control , Infecciones por Escherichia coli/veterinaria , Inmunización Pasiva , Inmunoglobulina G , Vacunas de Subunidad/efectos adversosRESUMEN
Resumen Objetivo: describir la presentación clínica, el diagnóstico y el tratamiento quirúrgico de un paciente con síndrome de la arteria mesentérica superior o síndrome de Wilkie combinado con síndrome de cascanueces o síndrome de compresión de la vena renal izquierda, en un centro de alta complejidad de un país latinoamericano. Descripción del caso: paciente masculino de 25 años, procedente de Estados Unidos, quien consultó por un año de pérdida de peso y episodios de obstrucción intestinal de etiología desconocida tras múltiples estudios de imagen. Se le realizaron estudios endoscópicos sin hallazgos; en la sala de recuperación desarrolló dolor abdominal que requirió ingreso al servicio de urgencias. La enterotomografía mostró dilatación de asas de colon e intestino delgado, con disminución del ángulo aortomesentérico y la serie gastrointestinal con paso filiforme del medio de contraste. Se intentó el manejo conservador como terapia inicial, con intolerancia al soporte nutricional entérico. Finalmente, se optó por el tratamiento quirúrgico, con un proceso de recuperación tórpido inicialmente, pero al final con resolución de los síntomas y aumento de peso. Conclusión: el síndrome de Wilkie es una enfermedad rara y un desafío diagnóstico en pacientes con pérdida de peso y dolor abdominal. Describimos un caso de compresión de la arteria mesentérica superior en el que se logró el diagnóstico con múltiples estrategias diagnósticas y resolución completa luego del tratamiento quirúrgico. La disminución del ángulo aortomesentérico puede comprimir la arteria mesentérica superior, así como la vena renal izquierda, que en ese caso resultó en un síndrome combinado de Wilkie y de cascanueces.
Abstract Objective: to describe the clinical presentation, diagnosis, and surgical treatment of a patient with superior mesenteric artery syndrome or Wilkie syndrome combined with the nutcracker syndrome or left renal vein compression syndrome in a tertiary referral center in a Latin American country. Case description: a 25-year-old male patient from the United States who attended for a year of weight loss and intestinal obstruction episodes of unknown etiology after multiple imaging studies. Endoscopic studies were performed without findings. While in the recovery room, he developed abdominal pain requiring admission to the emergency service. The CT enterography showed dilation of the colon loops and small intestine with a decrease of the aortomesenteric (AOM) angle and the gastrointestinal series with the filiform passage of the contrast medium. Conservative management was attempted as initial therapy with intolerance to enteric nutritional support. Finally, we initially opted for surgical treatment, with a slow recovery process, but in the end, with a resolution of symptoms and weight gain. Conclusion: Wilkie syndrome is a rare disease and a diagnostic challenge in patients with weight loss and abdominal pain. We described a superior mesenteric artery compression case in which diagnosis was achieved with multiple diagnostic strategies and complete resolution after surgical treatment. The decreased aortomesenteric angle may compress the superior mesenteric artery and the left renal vein. In this case, it resulted in a combined Wilkie and nutcracker syndrome.
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The Mexican wolf (Canis lupus baileyi) was once distributed in southern United States and northern Mexico. It is an endangered subspecies detached from the gray wolf, and likely exemplifies one of the original migration waves of C. lupus into the new world. This is a canine whose individuals survive in specialized facilities, zoos, and museums as part of captive-breeding programs. In order to contribute to the improvement of the management of this species and favor its long-term conservation in Mexico, we aimed to evaluate the diversity and abundance of the fecal bacterial microbiota in two populations exposed to different types of diet: (1) Michilia (23° N, 104° W); kibble daily and raw meat sporadically, and (2) Ocotal (19° N, 99° W); raw meat daily and live animals periodically. Next generation sequencing (V3-V4 16S rRNA gene) by Illumina was implemented. The operational taxonomic units (OTUs) in Michilia resulted in 9 phyla, 19 classes, 34 orders, 61 families, 204 genera, and 316 species, while in Ocotal there were 12 phyla, 24 classes, 37 orders, 69 families, 232 genera, and 379 species. Higher estimated Chao1 richness, Shannon diversity, and core microbiota were observed in Ocotal. Differences (p < 0.05) between populations occurred according to the Bray-Curtis beta diversity index. In the Michilia, dominance of bacteria that degrade carbohydrates (Firmicutes, Lachnospiraceae, Blautia, Clostrodium, Eisenbergiella, Romboutsia, and Ruminococcus) was observed; they are abundant in kibble diets. In contrast, the Ocotal microbiota was dominated by protein-degrading bacteria (Fusobacteria, Fusobacteriaceae, and Fusobacteria), indicating a possible positive relation with a raw meat diet. The information generated in this study is fundamental to support the implementation of better management plans in the two populations considered here, as well as in different facilities of southern United States and Mexico, where this subspecies is kept in captivity for conservation purposes.
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The general bacterial microbiota of the soft tick Ornithodoros turicata found on Bolson tortoises (Gopherus flavomarginatus) were analyzed using next generation sequencing. The main aims of the study were to establish the relative abundance of bacterial taxa in the tick, and to document the presence of potentially pathogenic species for this tortoise, other animals, and humans. The study was carried-out in the Mapimi Biosphere Reserve in the northern-arid part of Mexico. Bolson tortoises (n = 45) were inspected for the presence of soft ticks, from which 11 tortoises (24.4%) had ticks in low loads (1-3 ticks per individual). Tick pools (five adult ticks each) were analyzed through 16S rRNA V3-V4 region amplification in a MiSeq Illumina, using EzBioCloud as a taxonomical reference. The operational taxonomic units (OTUs) revealed 28 phyla, 84 classes, 165 orders, 342 families, 1013 genera, and 1326 species. The high number of taxa registered for O. turicata may be the result of the variety of hosts that this tick parasitizes as they live inside G. flavomarginatus burrows. While the most abundant phyla were Proteobacteria, Actinobacteria, and Firmicutes, the most abundant species were two endosymbionts of ticks (Midichloria-like and Coxiella-like). Two bacteria documented as pathogenic to Gopherus spp. were registered (Mycoplasma spp. and Pasteurella testudinis). The bovine and ovine tick-borne pathogens A. marginale and A. ovis, respectively, were recorded, as well as the zoonotic bacteria A. phagocytophilum,Coxiella burnetii, and Neoehrlichia sp. Tortoises parasitized with O. turicata did not show evident signs of disease, which could indicate a possible ecological role as a reservoir that has yet to be demonstrated. In fact, the defense mechanisms of this tortoise against the microorganisms transmitted by ticks during their feeding process are still unknown. Future studies on soft ticks should expand our knowledge about what components of the microbiota are notable across multiple host-microbe dynamics. Likewise, studies are required to better understand the host competence of this tortoise, considered the largest terrestrial reptile in North America distributed throughout the Chihuahuan Desert since the late Pleistocene.
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Shiga toxin-producing Escherichia coli (STEC) cause diarrhea and dysentery, which may progress to hemolytic uremic syndrome (HUS). Vaccination has been proposed as a preventive approach against STEC infection; however, there is no vaccine for humans and those used in animals reduce but do not eliminate the intestinal colonization of STEC. The OmpT, Cah and Hes proteins are widely distributed among clinical STEC strains and are recognized by serum IgG and IgA in patients with HUS. Here, we develop a vaccine formulation based on two chimeric antigens containing epitopes of OmpT, Cah and Hes proteins against STEC strains. Intramuscular and intranasal immunization of mice with these chimeric antigens elicited systemic and local long-lasting humoral responses. However, the class of antibodies generated was dependent on the adjuvant and the route of administration. Moreover, while intramuscular immunization with the combination of the chimeric antigens conferred protection against colonization by STEC O157:H7, the intranasal conferred protection against renal damage caused by STEC O91:H21. This preclinical study supports the potential use of this formulation based on recombinant chimeric proteins as a preventive strategy against STEC infections.
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Redox reactions are ubiquitous in biological processes. Enzymes involved in redox metabolism often use cofactors in order to facilitate electron-transfer reactions. Common redox cofactors include micronutrients such as vitamins and metals. By far, while iron is the main metal cofactor, riboflavin is the most important organic cofactor. Notably, the metabolism of iron and riboflavin seem to be intrinsically related across life kingdoms. In bacteria, iron availability influences expression of riboflavin biosynthetic genes. There is documented evidence for riboflavin involvement in surpassing iron-restrictive conditions in some species. This is probably achieved through increase in iron bioavailability by reduction of extracellular iron, improvement of iron uptake pathways and boosting hemolytic activity. In some cases, riboflavin may also work as replacement of iron as enzyme cofactor. In addition, riboflavin is involved in dissimilatory iron reduction during extracellular respiration by some species. The main direct metabolic relationships between riboflavin and iron in bacterial physiology are reviewed here.
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Shiga Toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens associated with diarrhea, dysentery, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). Shiga toxins are the major virulence factor of these pathogens, however adhesion and colonization to the human intestine is required for STEC pathogenesis. A subset of STEC strains carry the Locus of Enterocyte Effacement (LEE) pathogenicity island (PAI), which encodes genes that mediate the colonization of the human intestine. While LEE-positive STEC strains have traditionally been associated with human disease, the burden of disease caused by STEC strains that lacks LEE (LEE-negative) has increased recently in several countries; however, in the absence of LEE, the molecular pathogenic mechanisms by STEC strains are unknown. Here we report a 86-kb mosaic PAI composed of four modules that encode 80 genes, including novel and known virulence factors associated with adherence and autoaggregation. Therefore, we named this PAI as Locus of Adhesion and Autoaggregation (LAA). Phylogenomic analysis using whole-genome sequences of STEC strains available in the NCBI database indicates that LAA PAI is exclusively present in a subset of emerging LEE-negative STEC strains, including strains isolated from HC and HUS cases. We suggest that the acquisition of this PAI is a recent evolutionary event, which may contribute to the emergence of these STEC.
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Adhesinas Bacterianas/genética , Infecciones por Escherichia coli/microbiología , Sitios Genéticos , Islas Genómicas , Escherichia coli Shiga-Toxigénica/genética , Factores de Virulencia/genética , Biología Computacional , Genoma Bacteriano , Humanos , Filogenia , Escherichia coli Shiga-Toxigénica/clasificaciónRESUMEN
The most common mechanism of trimethoprim (TMP)-resistance is the acquisition of dihydrofolate reductase enzyme resistant to this drug. Previous molecular characterization of TMP-genes resistance in Chilean isolates of Shigella sonnei searching for dfrA1 and dfrA8, showed solely the presence of dfrA8 (formerly dhfrIIIc). However, these genetic markers were absent in S. sonnei strains further isolated during an outbreak in 2009. To identify the TMP-resistance gene in these strains, a genomic DNA library from a TMP-resistant (TMP(R)) S. sonnei representative strain for the outbreak was used to clone, select and identify a TMP-resistance marker. The TMP(R) clone was sequenced by primer walking, identifying the presence of the dfrA14 gene in the sul2-strA'-dfrA14-'strA-strB gene arrangement, harbored in a native 6779-bp plasmid. The same plasmid was isolated by transforming with a ~4.2 MDa plasmid extracted from several TMP(R) S. sonnei strains into Escherichia coli. This plasmid, named pABC-3, was present only in dfrA14-positive strains and was homologous to a previously described pCERC-1, but different due to the absence of an 11-bp repetitive unit. The distribution of dfrA1, dfrA8, and dfrA14 TMP-resistance genes was determined in 126 TMP(R) S. sonnei isolates. Most of the strains (96%) carried only one of the three TMP-resistance genes assessed. Thus, all strains obtained during the 2009-outbreak harbored only dfrA14, whereas, dfrA8 was the most abundant gene marker before outbreak and, after the outbreak dfrA1 seems have appeared in circulating strains. According to PFGE, dfrA14-positive strains were clustered in a genetically related group including some dfrA1- and dfrA8-positive strains; meanwhile other genetic group included most of the dfrA8-positive strains. This distribution also correlated with the isolation period, showing a dynamics of trimethoprim genetic markers prevalent in Chilean S. sonnei strains. To our knowledge, dfrA14 gene associated to a small non-conjugative plasmid was detected for the first time in Shigella. Apparently, the strain causing the outbreak must have been introduced, changing drastically the genetic distribution of trimethoprim resistance in Chilean S. sonnei strains.
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Genes Bacterianos , Plásmidos , Shigella sonnei/efectos de los fármacos , Shigella sonnei/genética , Tetrahidrofolato Deshidrogenasa/genética , Resistencia al Trimetoprim , Chile/epidemiología , Clonación Molecular , Brotes de Enfermedades , Disentería Bacilar/epidemiología , Disentería Bacilar/microbiología , Orden Génico , Transferencia de Gen Horizontal , Humanos , Análisis de Secuencia de ADN , Shigella sonnei/aislamiento & purificaciónRESUMEN
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1') in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1' gene (pVAXefa-1') into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1', EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti-EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10, and IFN-γ were observed upon re-stimulation with either heat-killed bacteria or EHEC-secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1' have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle.
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Toxinas Bacterianas/inmunología , Infecciones por Escherichia coli/prevención & control , Escherichia coli O157/inmunología , Proteínas de Escherichia coli/inmunología , Vacunas contra Escherichia coli/inmunología , Vacunas de ADN/inmunología , Administración Intranasal , Animales , Anticuerpos Antibacterianos/sangre , Carga Bacteriana , Toxinas Bacterianas/genética , Líquido del Lavado Bronquioalveolar/química , Proliferación Celular , Modelos Animales de Enfermedad , Infecciones por Escherichia coli/inmunología , Escherichia coli O157/genética , Proteínas de Escherichia coli/genética , Vacunas contra Escherichia coli/administración & dosificación , Vacunas contra Escherichia coli/genética , Humanos , Inmunoglobulina A Secretora/análisis , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Intestinos/microbiología , Ratones Endogámicos C57BL , Cavidad Nasal/química , Plásmidos , Linfocitos T/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/genéticaRESUMEN
Los modelos de desarrollo constituyen una forma de organización de los estados que responden a una corriente de pensamiento, lógicamente cada modelo de desarrollo es implícito a un modelo de estado y a su vez este modelo de estado, presentará ciertas características que influirán en todos los ámbitos de los individuos que hacen vida dentro de esta sociedad, la forma de concebir la salud y consecuentemente el quehacer en salud no escapa a esto; es así que podremos ver como cada concepción de salud se corresponde con un modelo de desarrollo y a una práctica que la caracteriza.
Development models are a way of organization of states that match a current of thought, logically each development model is implicit to onestate model and in turn this state model will present certain characteristics that will affect all areas of the individuals that live in this society, the way of thinking about health and consequently the task in health is no exception to this, so we can see how each health concept corresponds to a model of development and practice that characterize.
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Humanos , Masculino , Femenino , Conocimientos, Actitudes y Práctica en Salud , Modelos Organizacionales , Política de Salud , Estado , Desarrollo Económico , Fuerza Laboral en Salud , Servicios de Salud/legislación & jurisprudenciaRESUMEN
BACKGROUND: Congenital syphilis (CS) is a major global public health problem. Buenaventura, a socioeconomically deprived municipality in the Colombian Pacific Coast, accounts for 6.6% of all CS cases in Colombia. To begin to understand the main reasons for the high rates of the disease in Buenaventura, we conducted a retrospective electronic health record analysis of all infants admitted with CS during the first 7 months of 2011 to the Hospital Departamental de Buenaventura, the city's main birthing hospital. METHODS: The diagnosis of gestational syphilis and CS was based on a predefined Colombian public health service algorithm. Clinical, laboratory, and sociodemographic parameters for all infants studied, including maternal access to prenatal care, syphilis serologic diagnosis, and adequacy of penicillin treatment, were abstracted and analyzed. RESULTS: A total of 89 infants met the case definition for CS. Most mothers (80%) were affiliated with government-regulated or private health care insurance plans. While 64 (70%) of 92 attended at least 1 antenatal care visit and 59 of these 64 (84%) were screened for syphilis, only 5 (8%) of 59 received appropriate antibiotic therapy. Although most infants were asymptomatic at birth, prematurity (15/82) was common. Two infants died in the neonatal period, and 5 pregnancies ended in stillbirth. CONCLUSIONS: Our findings confirm that Buenaventura has a very high incidence of CS and demonstrate that existing antenatal care gestational syphilis programs are flawed. Prevention strategies should emphasize enhanced early syphilis screening in pregnancy, preferably through the implementation of point-of-care testing in the community and same-day treatment with at least 1 dose of penicillin.
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Antibacterianos/uso terapéutico , Penicilina G/uso terapéutico , Sistemas de Atención de Punto , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/microbiología , Sífilis Congénita/epidemiología , Treponema pallidum/aislamiento & purificación , Adolescente , Adulto , Colombia/epidemiología , Esquema de Medicación , Femenino , Estudios de Seguimiento , Política de Salud , Humanos , Incidencia , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Salud Pública , Estudios Retrospectivos , Vigilancia de Guardia , Factores Socioeconómicos , Sífilis Congénita/tratamiento farmacológicoRESUMEN
BACKGROUND: The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum (Tp) to escape immune recognition while simultaneously inducing inflammation. METHODS: To better understand the duality of immune evasion and immune recognition in human syphilis, herein we used a combination of flow cytometry, immunohistochemistry (IHC), and transcriptional profiling to study the immune response in the blood and skin of 27 HIV(-) SS patients in relation to spirochetal burdens. Ex vivo opsonophagocytosis assays using human syphilitic sera (HSS) were performed to model spirochete-monocyte/macrophage interactions in vivo. RESULTS: Despite the presence of low-level spirochetemia, as well as immunophenotypic changes suggestive of monocyte activation, we did not detect systemic cytokine production. SS subjects had substantial decreases in circulating DCs and in IFNγ-producing and cytotoxic NK-cells, along with an emergent CD56-/CD16+ NK-cell subset in blood. Skin lesions, which had visible Tp by IHC and substantial amounts of Tp-DNA, had large numbers of macrophages (CD68+), a relative increase in CD8+ T-cells over CD4+ T-cells and were enriched for CD56+ NK-cells. Skin lesions contained transcripts for cytokines (IFN-γ, TNF-α), chemokines (CCL2, CXCL10), macrophage and DC activation markers (CD40, CD86), Fc-mediated phagocytosis receptors (FcγRI, FcγR3), IFN-ß and effector molecules associated with CD8 and NK-cell cytotoxic responses. While HSS promoted uptake of Tp in conjunction with monocyte activation, most spirochetes were not internalized. CONCLUSIONS: Our findings support the importance of macrophage driven opsonophagocytosis and cell mediated immunity in treponemal clearance, while suggesting that the balance between phagocytic uptake and evasion is influenced by the relative burdens of bacteria in blood and skin and the presence of Tp subpopulations with differential capacities for binding opsonic antibodies. They also bring to light the extent of the systemic innate and adaptive immunologic abnormalities that define the secondary stage of the disease, which in the skin of patients trends towards a T-cell cytolytic response.
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Sangre/inmunología , Evasión Inmune , Piel/inmunología , Sífilis/inmunología , Sífilis/microbiología , Treponema pallidum/inmunología , Treponema pallidum/patogenicidad , Adulto , Femenino , Citometría de Flujo , Perfilación de la Expresión Génica , Humanos , Inmunidad Celular , Inmunohistoquímica , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Proteínas Opsoninas/sangre , FagocitosisRESUMEN
Objetivo La evaluación de impacto de un programa comunitario algunas veces se basa en técnicas estadísticas como modelos de regresión lineal, y tiene como objetivo cuantificar su efecto sobre aspectos sociales o el bienestar general de la comunidad. No es frecuente utilizar técnicas estadísticas con estructura de correlación entre los sujetos evaluados que permitan modelar variables de tipo social, o sicológica. Esta estrategia de análisis incorpora más información y por lo tanto debe producir resultados más precisos. Métodos En este trabajo se muestra una evaluación de impacto de los efectos producidos sobre el nivel de depresión de una población participante de un grupo de acciones del INDER Medellín en el año 2005, usando modelos lineales mixtos. Resultados Se identificaron variables importantes que reflejan resultados de impacto positivos, como el tiempo de intervención y la edad. Conclusiones Participar en las actividades de bienestar del INDER contribuye a disminuir los niveles de depresión.(AU)
Objective Statistical techniques such as linear regression models are sometimes used for evaluating a community programme's impact, especially when the goal is to quantify its effects on social aspects or a particular community's overall welfare. Statistical techniques taking intra-subject correlation into account, thereby allowing social or psychological variables to be modelled, are not normally used. Such modelling strategy takes more information into account and must thus yield more accurate results than those based solely on linear regression models. Methods This paper evaluates (by means of a linear mixed model) the impact of an Institute of Sport and Recreation (Instituto de Deportes y Recreación - INDER) programme run in 2005 in Medellín on a participating population's levels of depression. Results Important variables such us intervention time and age were identified as important predictors which led to reducing depression. Conclusions Participating in INDER´s welfare programme contributed towards reducing levels of depression.(AU)
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Humanos , Adulto , Salud Mental , Depresión/epidemiología , Promoción de la Salud , Modelos Lineales , Colombia/epidemiología , Estudios de Evaluación como AsuntoRESUMEN
OBJECTIVES: To determine factors influencing the age at onset of rheumatoid arthritis (RA). METHODS: A sample of 152 Colombian patients was investigated. Hazard ratios (HRs) that measured the effect size of risk factors on the age at RA onset were computed by using Cox regression models. RESULTS: Positive anti-CCP antibodies were associated with an increased risk of early RA onset (HR = 1.60; 95% confidence interval, [1.06, 2.4]), whereas the presence of the protective (70)DERAA(74) sequence was associated with a delayed onset (HR = 0.55; [0.33, 0.92]). After controlling for both anti-CCP antibodies and the (70)DERAA(74) sequence, the following variables did not influence significantly the age at RA onset: gender, ever cigarette smoking, family RA history, the TNF-308 A polymorphism, HLA shared epitope, and the presence of rheumatoid factor. CONCLUSION: Anti-CCP antibodies and the HLA-DRB1 (70)DERAA(74) sequence influence the age at onset of RA.
Asunto(s)
Anticuerpos Antiidiotipos/sangre , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inmunología , Péptidos Cíclicos/inmunología , Adulto , Edad de Inicio , Artritis Reumatoide/genética , Colombia , Femenino , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Análisis de Regresión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18-68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer > or = 1 : 4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.
Asunto(s)
Sífilis Cutánea/epidemiología , Sífilis Cutánea/patología , Treponema pallidum/aislamiento & purificación , Adolescente , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Análisis por Conglomerados , Estudios de Cohortes , Colombia/epidemiología , Dermatoglifia del ADN , ADN Polimerasa I/genética , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Enfermedades Endémicas , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Reaginas/sangre , Piel/microbiología , Piel/patología , Sífilis Cutánea/microbiología , Treponema pallidum/clasificación , Treponema pallidum/genética , Adulto JovenRESUMEN
OBJECTIVES: A study was conducted to assess the prevalence of maternal syphilis and estimate the rate of congenital syphilis in five rural villages surrounding Jeremie, Haiti. METHODS: This research was a retrospective observational study. Data were extracted from the Haitian Health Foundation's public health database and verified through original clinical paper records, death certificates, midwife reports, and discussions with community health workers. Data were analyzed by chi-square analysis, bivariate correlations, and two-tailed t-test for independent samples. RESULTS: Of the 410 women tested for syphilis, 31 (7.6 percent) were sero-reactive. Average gestation at time of testing was 25 weeks, which correlated with entry into prenatal care at an average of 23 weeks. Women who tested positive during pregnancy were more likely to have had a negative pregnancy outcome than those who did not (chi square = 16.4; P < 0.0001). The estimated rate of congenital syphilis in the region was 767 per 100,000 live births. CONCLUSIONS: Maternal syphilis is prevalent in rural Haiti. This prevalence combined with late entry into prenatal care contributes to adverse pregnancy outcomes and a high estimated rate of congenital syphilis. More research is needed on congenital syphilis and prenatal-care-seeking practices of rural Haitian women in order to understand the impact of maternal syphilis in the region and improve pregnancy outcomes.
OBJETIVOS: Evaluar la prevalencia de sífilis materna y estimar la tasa de sífilis congénita en cinco poblaciones rurales cercanas a Jeremie, Haití. MÉTODOS: Estudio observacional retrospectivo a partir de datos extraídos de la base de datos de salud pública de la Fundación Haitiana de Salud y verificada con los registros clínicos originales en papel, los certificados de defunción, los informes de las parteras y discusiones con los trabajadores comunitarios de salud. Los datos se analizaron mediante la prueba de la ji al cuadrado, correlaciones bifactoriales y la prueba de la t de dos colas para muestras independientes. RESULTADOS: De las 410 mujeres sometidas a la prueba de sífilis, 31 (7,6 por ciento) resultaron seropositivas. La edad gestacional promedio al momento de la prueba fue de 25 semanas, lo que se correlacionó con la edad gestacional de entrada a la atención prenatal (23 semanas). Las mujeres que resultaron seropositivas durante el embarazo presentaron mayor probabilidad de tener un desenlace negativo de su embarazo que las mujeres que resultaron seronegativas (χ2 = 16,4; P < 0,0001). La tasa estimada de sífilis congénita en la zona fue de 767 por 100000 nacidos vivos. CONCLUSIONES: La sífilis materna es frecuente en las zonas rurales de Haití, lo que combinado con la entrada tardía a los servicios de atención prenatal, contribuye a los desenlaces adversos de los embarazos y a la alta tasa estimada de sífilis congénita. Se requieren más estudios sobre la sífilis congénita y los hábitos de búsqueda de atención prenatal de las mujeres de zonas rurales de Haití para comprender el impacto de la sífilis materna en esta parte del país y mejorar el desenlace de los embarazos.