Detection of Genes Related to Antibiotic Resistance in Leptospira.

Leptospirosis is a disease caused by the bacteria of the Leptospira genus, which can usually be acquired by humans through contact with urine from infected animals; it is also possible for this urine to contaminate soils and bodies of water. The disease can have deadly consequences in some extreme cases. Fortunately, until now, patients with leptospirosis have responded adequately to treatment with doxycycline and azithromycin, and no cases of antibiotic resistance have been reported. However, with the extensive use of such medications, more bacteria, such as Staphylococci and Enterococci, are becoming resistant. The purpose of this study is to determine the presence of genes related to antibiotic resistance in the Leptospira genus using bioinformatic tools, which have not been undertaken in the past. Whole genomes from the 69 described Leptospira species were downloaded from NCBI's GeneBank and analyzed using CARD (The Comprehensive Antibiotic Resistant Database) and RAST (Rapid Annotations using Subsystem Technology). After a detailed genomic search, 12 genes associated with four mechanisms were found: resistance to beta-lactamases, vancomycin, aminoglycoside adenylyltransferases, as well as multiple drug efflux pumps. Some of these genes are highly polymorphic among different species, and some of them are present in multiple copies in the same species. In conclusion, this study provides evidence of the presence of genes related to antibiotic resistance in the genomes of some species of the genus Leptospira, and it is the starting point for future experimental evaluation to determine whether these genes are transcriptionally active in some species and serovars.

Mutaciones en los genes PDGFRA, KIT y KDR en pacientes con glioblastoma se relacionan con un peor desenlace / Mutations in the PDGFRA, KIT, and KDR genes in patients with glioblastoma are associated with a worse outcome

Resumen Introducción: existen varios Receptores Tirosina Quinasa que están involucrados en el desarrollo, crecimiento y progresión de las células tumorales, por ejemplo, en los glioblastomas se ha encontrado que por un posible desequilibrio de ligamiento los genes PDGFRA, KIT y KDR, ubicados en el brazo largo del cromosoma 4 (4q11-q12), podrían estar relacionados con la progresión de esta neoplasia. Objetivo: reportar dos casos clínicos de pacientes con diagnóstico de glioblastoma y mutaciones en los genes PDGFRA, KIT, KDR, y su relación con un peor desenlace. Casos clínicos: en este artículo se presenta el caso de dos pacientes con glioblastomas que presentan mutaciones en los genes anteriormente mencionados resultado de la secuenciación de un panel genético que evalúa 324 genes y 37 fusiones génicas y la progresión clínica acelerada durante el transcurso de la enfermedad. Conclusión: los cambios producidos en los glioblastomas por las mutaciones en los receptores tirosina quinasa a nivel biológico podrían describir una mayor capacidad proliferativa del tumor, lo que en el ámbito clínico se ha evidenciado como un peor pronóstico para el paciente, de ahí nace la necesidad de tener paneles genéticos que ayuden a identificar el perfil tumoral, e incentivar más estudios clínicos relacionados a fármacos que tengan como objetivo dichos receptores.

Abstract Introduction: there are several Tyrosine Kinase Receptors that are involved in the development, growth and progression of tumor cells, for example, in glioblastomas it has been found that due to a possible linkage imbalance the PDGFRA, KIT and KDR genes, located in the arm length of chromosome 4 (4q11-q12), which could be related to the progression of this neoplasm. Objective: to report two clinical cases of patients diagnosed with glioblastoma and mutations in the PDGFRA, KIT, and KDR genes, and their relationship with a worse outcome. Clinical cases: this article presents the case of two patients with mutations in the genes, the result of a genetic panel that evaluated 324 genes and 37 gene fusions and accelerated clinical progression during the course of the disease. Conclusion: the changes produced in glioblastomas by mutations in receptor tyrosine kinases at the biological level describe a greater proliferative capacity of the tumor, which in the clinical setting has been evidenced as a worse prognosis for the patient, hence the need for have genetic panels that help identify the tumor profile and encourage more clinical studies related to drugs that target those receptors.

Narrative review of generalities of the genus Leptospira and its virulence factors associated with renal pathophysiology

Worldwide, leptospirosis is the most highly prevalent zoonosis. Although the wide range of clinical manifestations of leptospirosis in humans is well-documented, knowledge of the mechanisms through which this pathogen causes kidney disease remains limited. This narrative review of the scientific literature presents experimental studies of pathophysiology and kidney disease in leptospirosis, both in humans and animals, and the results show that virulence factors are involved in kidney damage by inducing interstitial tubular nephritis, which is the most frequent pathological manifestation, additionally, to the acute non-oliguric renal lesion with hypokalemia, and loss of magnesium and sodium. Finally, it is concluded that in leptospirosis, the initial lesion in the kidney is caused by damage to the cell membrane of the proximal tubular region cells by pathogenic Leptospira virulence factors, thus exacerbating the immune response

Evidencia molecular de Leptospira interrogans sensu stricto en Cavia porcellus (cuyes) destinados para el consumo humano en el municipio de Pasto, Nariño / Molecular evidence of Leptospira interrogans sensu stricto in Cavia porcellus (guinea pig) grown for human consumption in Pasto, Nariño

Introducción: La leptospirosis es una zoonosis emergente, endémica en Colombia, que afecta tanto animales domésticos como silvestres. Es considerada de riesgo laboral, ya que la transmisión al ser humano está asociada a la exposición con animales o ambientes infectados. En el departamento de Nariño, la producción de cuyes para el consumo humano se realiza en sistemas de crianza tradicionales que podrían favorecer la infección por Leptospira interrogans en esta especie. Objetivo: Detectar molecularmente la infección natural por especies patógenas del género Leptospira en cuyes que son destinados para el consumo humano en el municipio de Pasto. Materiales y métodos: Se tomaron 270 muestras de tejido renal en cuyes sacrificados en dos mataderos. Las muestras fueron analizadas mediante Reacción en Cadena de la Polimerasa (PCR) convencional y coloración diferencial de Warthin Starry (W-S). Resultados: En la evaluación de las 270 muestras, 4 (1,5%) fueron positivas para PCR y una de las muestras demostró la presencia de Leptospira bajo tinción W-S. Conclusiones: Mediante el uso de técnicas moleculares se evidenció L. interrogans en el tejido renal de Cavia porcellus. La circulación del patógeno en esta población representa un riesgo de infección para humanos y animales domésticos en contacto con estos sistemas productivos.

Introduction: Leptospirosis is an emerging zoonosis that is endemic in Colombia and affects both domestic and wild animals. It is considered an occupational risk since human transmission is associated with exposure to infected animals or environments. In the department of Nariño, the production of guinea pigs for human consumption applies traditional rearing systems that could cause animals to get infected with Leptosipira interrogans. Objective: To molecularly identify natural infection by pathogenic species of the genus Leptospira in guinea pigs used for human consumption in the municipality of Pasto (Colombia). Materials and methods: 270 kidney tissue samples were taken from guinea pigs slaughtered in two facilities. Samples were analyzed through conventional polymerase chain reaction (PCR) and Warthin Starry (W-S) differential staining. Results: While 4 (1.5%) out of the 270 samples were categorized as positive using PCR, only 1 sample showed the presence of Leptospira through W-S staining. Conclusions: Molecular techniques were useful to identify L. interrogans in kidney tissue of Cavia porcellus. Dissemination of this pathogen within this population represents an infection risk for humans and domestic animals that are in close proximity to these productive systems.

High Diversity of Leptospira Species Infecting Bats Captured in the Urabá Region (Antioquia-Colombia).

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the genus Leptospira. This zoonotic disease affects humans, domestic animals and wild animals. Colombia is considered an endemic country for leptospirosis; Antioquia is the second department in Colombia, with the highest number of reported leptospirosis cases. Currently, many studies report bats as reservoirs of Leptospira spp. but the prevalence in these mammals is unknown. The goal of this study was to better understand the role of bats as reservoir hosts of Leptospira species and to evaluate the genetic diversity of circulating Leptospira species in Antioquia-Colombia. We captured 206 bats in the municipalities of Chigorodó (43 bats), Carepa (43 bats), Apartadó (39 bats), Turbo (40 bats), and Necoclí (41 bats) in the Urabá region (Antioquia-Colombia). Twenty bats tested positive for Leptospira spp. infection (20/206-9.70%) and the species of infected bats were Carollia perspicillata, Dermanura rava, Glossophaga soricina, Molossus molossus, Artibeus planirostris, and Uroderma convexum. These species have different feeding strategies such as frugivorous, insectivores, and nectarivores. The infecting Leptospira species identified were Leptospira borgpetersenii (3/20-15%), Leptospira alexanderi (2/20-10%), Leptospira noguchii (6/20-30%), Leptospira interrogans (3/20-15%), and Leptospira kirschneri (6/20-30%). Our results showed the importance of bats in the epidemiology, ecology, and evolution of Leptospira in this host-pathogen association. This is the first step in deciphering the role played by bats in the epidemiology of human leptospirosis in the endemic region of Urabá (Antioquia-Colombia).

Deficiencia selectiva de inmunoglobulina A: manifestaciones clínicas, hallazgos de laboratorio y diagnóstico preciso / Selective Immunoglobulin A deficiency: clinical manifestations, laboratory findings and accurate diagnosis

Resumen La inmunoglobulina A (IgA) es el isotipo de anticuerpo más abundante en los humanos y fundamentalmente participa en la defensa contra las infecciones y el desarrollo de la tolerancia inmune en las mucosas. La deficiencia de IgA es la inmunodeficiencia más frecuente en humanos, pero comúnmente es asintomática y transitoria. Para diagnosticarla, se cuantifica la concentración de IgA en sangre y se evalúa la magnitud de su disminución. De acuerdo con esta evaluación se clasifica en deficiencia parcial (DPIgA) o deficiencia total (DTIgA). Adicionalmente, si solo se afectan los niveles de IgA sin alteraciones de otras inmunoglobulinas séricas como IgM e IgG o subclases de inmunoglobulina G, entonces se denomina como deficiencia selectiva de IgA (DSIgA). La deficiencia selectiva de IgA es de mayor relevancia clínica y considerada un error innato de la inmunidad, aunque su etiología aún es desconocida y clínicamente se asocia a infecciones de los tractos respiratorio y gastrointestinal, alergias y manifestaciones autoinmunes. Se realizó una búsqueda de artículos científicos en PubMed, Scopus, SciELO y Redalyc sobre la deficiencia selectiva de inmunoglobulina A, con el objetivo de realizar una revisión temática sobre las manifestaciones clínicas, el diagnóstico y el adecuado manejo clínico de los pacientes con esta inmunodeficiencia. Se propone un nuevo algoritmo clínico con el objetivo de mejorar el diagnóstico y brindar un adecuado manejo clínico de los pacientes con esta inmunodeficiencia. Un paciente con deficiencia selectiva de IgA se caracteriza por infecciones recurrentes de los tractos gastrointestinal y respiratorio, en asociación con manifestaciones alérgicas y autoinmunes en individuos mayores de cuatro años, con niveles de IgA sérica menores de 7 mg/dL y con niveles normales de IgG e IgM, y en quienes se hayan descartado defectos relacionados con los linfocitos T u otras causas de hipogammaglobulinemia. Con respecto al manejo clínico, se deben ajustar los esquemas de vacunación e implementar profilaxis antibiótica en las infecciones graves y recurrentes. Para mejorar el pronóstico se debe realizar una atención del paciente por un equipo médico interdisciplinario y un seguimiento continuo por un prolongado periodo de tiempo.

Abstract Immunoglobulin A (IgA) is the most abundant antibody isotype in humans and participates in protection against infections and the development of immune tolerance in mucous membranes. IgA deficiency is the most common immunodeficiency in humans, but it is commonly asymptomatic and transient. To diagnose it, the concentration of IgA in blood is quantified and the magnitude of its decrease is evaluated. According to this evaluation, it is classified as partial deficiency (DPIgA) or total deficiency (DTIgA). Additionally, if only IgA levels are affected without alterations in other serum immunoglobulins such as IgM and IgG or subclasses of IgG, then it is referred to as selective IgA deficiency (DSIgA). Selective IgA deficiency is of greater clinical relevance and considered an innate immunity error, although its etiology is still unknown. This immunodeficiency is clinically associated with respiratory and gas- trointestinal tract infections, allergies and autoimmune manifestations. A search of scientific articles was conducted in bibliographic databases PubMed, Scopus, SciELO and Redalyc on selective immunoglobulin A deficiency. Our objective was to perform a review on clinical manifestations, diagnosis, and appropriate clinical management of patients with this immunodeficiency. A new clinical algorithm is proposed in order to improve the diagnosis and provide adequate clinical management of patients with this immunodeficiency. A patient with selective IgA deficiency is characterized by recurrent infections of the gastrointestinal and respiratory tracts, in association with allergic and autoimmune manifestations in individuals older than four years. Serum IgA levels are less than 7 mg/dL, with normal levels of IgG and IgM, and defects related to T lymphocytes or other causes of hypogammaglobulinemia have been ruled out. Regarding clinical management, vaccination schedules should be adjusted and antibiotic prophylaxis should be implemented in severe and recurrent infections. Additionally, to improve prognosis, patient care should be performed by an interdisciplinary medical team and continuous monitoring for a prolonged period of time.

Genetic diversity of Leptospira in northwestern Colombia: first report of Leptospira santarosai as a recognised leptospirosis agent.

The region of Antioquia in northeastern Colombia has the highest number of reported leptospirosis cases in the country. It also shows high seroprevalence indexes in the general population and socio-environmental conditions favourable for the transmission of the disease between humans and animals. In this study, 25 Leptospira isolates from Colombia's Antioquia department were identified to the species level as L. santarosai (12), L. interrogans (9) and L. meyeri (4) using phylogenetic analysis of the Amidohydrolase gene. Typing at the serovar level was performed using multilocus sequence typing (MLST) and monoclonal antibodies. The serovars Canalzonae, Babudieri, Alice, Beye, and Copenhageni have been identified as causing human or animal infections in Antioquia, Colombia. The four environmental isolates were not identified to the serovar level. L. santarosai serovar Canalzonae and Alice were identified as new etiologic agents of human leptospirosis in Antioquia, Colombia. This paper reports species and serovars that were previously unknown in the region.

Genetic diversity of Leptospira in northwestern Colombia: first report of Leptospira santarosai as a recognised leptospirosis agent

The region of Antioquia in northeastern Colombia has the highest number of reported leptospirosis cases in the country. It also shows high seroprevalence indexes in the general population and socio-environmental conditions favourable for the transmission of the disease between humans and animals. In this study, 25 Leptospira isolates from Colombia’s Antioquia department were identified to the species level as L. santarosai (12), L. interrogans (9) and L. meyeri (4) using phylogenetic analysis of the Amidohydrolase gene. Typing at the serovar level was performed using multilocus sequence typing (MLST) and monoclonal antibodies. The serovars Canalzonae, Babudieri, Alice, Beye, and Copenhageni have been identified as causing human or animal infections in Antioquia, Colombia. The four environmental isolates were not identified to the serovar level. L. santarosai serovar Canalzonae and Alice were identified as new etiologic agents of human leptospirosis in Antioquia, Colombia. This paper reports species and serovars that were previously unknown in the region.