Integrating Scalable Genome Sequencing Into Microbiology Laboratories for Routine Antimicrobial Resistance Surveillance.

Antimicrobial resistance (AMR) is considered a global threat, and novel drug discovery needs to be complemented with systematic and standardized epidemiological surveillance. Surveillance data are currently generated using phenotypic characterization. However, due to poor scalability, this approach does little for true epidemiological investigations. There is a strong case for whole-genome sequencing (WGS) to enhance the phenotypic data. To establish global AMR surveillance using WGS, we developed a laboratory implementation approach that we applied within the NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance. In this paper, we outline the laboratory implementation at 4 units: Colombia, India, Nigeria, and the Philippines. The journey to embedding WGS capacity was split into 4 phases: Assessment, Assembly, Optimization, and Reassessment. We show that on-boarding WGS capabilities can greatly enhance the real-time processing power within regional and national AMR surveillance initiatives, despite the high initial investment in laboratory infrastructure and maintenance. Countries looking to introduce WGS as a surveillance tool could begin by sequencing select Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens that can demonstrate the standardization and impact genome sequencing has in tackling AMR.

Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging public health problem. This study explores the specifics of CRKP epidemiology in Colombia based on whole genome sequencing (WGS) of the National Reference Laboratory at Instituto Nacional de Salud (INS)'s 2013-2017 sample collection. METHODS: A total of 425 CRKP isolates from 21 departments were analyzed by HiSeq-X10®Illumina high-throughput sequencing. Bioinformatic analysis was performed, primarily using the pipelines developed collaboratively by the National Institute for Health Research Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance (AMR), and AGROSAVIA. RESULTS: Of the 425 CRKP isolates, 91.5% were carbapenemase-producing strains. The data support a recent expansion and the endemicity of CRKP in Colombia with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates). We identified genes encoding carbapenemases blaKPC-3, blaKPC-2, blaNDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24, and various mobile genetic elements (MGE). The virulence of CRKP isolates was low, but colibactin (clb3) was present in 25.2% of isolates, and a hypervirulent CRKP clone (CG380) was reported for the first time in Colombia. ST258, ST512, and ST4851 were characterized by low levels of diversity in the core genome (ANI > 99.9%). CONCLUSIONS: The study outlines complex CRKP epidemiology in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific MGEs, while the other high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. The specifics of the Colombian situation stress the importance of WGS-based surveillance to monitor evolutionary trends of sequence types (STs), MGE, and resistance and virulence genes.

High prevalence of syndromic hearing loss in Mexican children undergoing cochlear implantation.

Objective: Studies evaluating genetic sensorineural hearing loss (SNHL) in Hispanic and Latino populations using genomic technologies are lacking. Recent data has shown that Hispanic and Latino children display lower genetic diagnostic rates despite similar prevalence rates of SNHL to their Asian and White counterparts, thus negatively affecting their clinical care. Our objective was to determine the genetic contribution to SNHL in a population of Mexican children undergoing evaluation for cochlear implantation. Methods: Pediatric patients from Mexico with severe to profound SNHL undergoing evaluation for cochlear implantation were recruited. Exome sequencing (ES) or hearing loss gene panel testing was performed. Variant pathogenicity was established in accordance to criteria established by the American College of Medical Genetics, and variants of interest were clinically confirmed via CLIA certified laboratory. Results: Genetic evaluation was completed for 30 Mexican children with severe to profound SNHL. A genetic cause was identified for 47% (14) of probands, and 7% (2) probands had an inconclusive result. Of the diagnoses, 10 (71%) were syndromic or likely syndromic, and 4 (29%) were nonsyndromic. Eight probands (80% of all syndromic diagnoses) were diagnosed with a syndromic form of hearing loss that mimics a nonsyndromic clinical presentation at a young age and so could not be suspected based on clinical evaluation alone without genetic testing. Conclusion: This is the largest study to date to use comprehensive genomic testing for the evaluation of Mexican children with severe to profound SNHL. A significant proportion of children in this cohort were diagnosed with syndromic hearing loss. Future study in a larger cohort of Mexican children with varying degrees of hearing loss is required to improve the efficacy of genetic testing and timely medical intervention within these ethnically diverse populations. Level of evidence: Level 4 (cohort study).

Calidad de la atención en salud en ataque cerebrovascular en un hospital de referencia en Colombia / Quality of health care in stroke in a reference hospital in Colombia

RESUMEN INTRODUCCIÓN: La evaluación de la calidad de la atención del ataque cerebrovascular (ACV) es una prioridad para los sistemas de salud, debido a su relación con la disminución de la discapacidad y la muerte. En este estudio se analizan los marcadores de calidad en ACV en un hospital de referencia en Nariño, Colombia. OBJETIVO: Evaluar los marcadores de calidad de atención en ACV en el Hospital Universitario Departamental de Nariño E. S. E., entre junio del 2018 y diciembre del 2019. Como referencia se comparó con los registros de Colombia en la plataforma RES-Q. MATERIALES Y MÉTODOS: Estudio descriptivo retrospectivo de pacientes con ACV atendidos intrahospitalariamente. La recolección de datos se realizó mediante la plataforma RES-Q, en tanto que el análisis se efectuó por medio de estadísticos descriptivos y frecuencias absolutas y relativas y las diferencias con pruebas analíticas. RESULTADOS: Se evaluaron 457 pacientes con predominio de ACV isquémico y se llevó a cabo trombólisis endovenosa al 7,2% en el 2018 y al 9,2 % en el 2019, el 27,7 % con tiempo puerta aguja menor a 60 minutos en el 2018 y el 42,8 % en el 2019. Entre los marcadores de calidad, se encontró mejoría en realización de NIHSS, evaluación de disfagia en las primeras 24 horas, realización de doppler carotideo en los primeros siete días. En comparación con Colombia, se encontró un porcentaje inferior en trombólisis endovenosa y trombectomía. La mayoría de los indicadores de atención en ACV es similar al promedio nacional. CONCLUSIONES: La mejoría en el cumplimiento de marcadores de calidad en ACV refleja el impacto de programas de atención en ACV. El monitoreo de los parámetros de calidad permite generar programas para fortalecer la atención integral del ataque cerebrovascular en la región.

ABSTRACT INTRODUCTION: The evaluation of the quality of care for Stroke is a priority for health systems, given its relationship with disability and death. In this study, Stroke quality markers are analyzed in stroke in a referral hospital in Narino, Colombia. OBJECTIVE: To evaluate the markers of quality of care in stroke in the Hospital Departamental Universitario de Narino E.S.E between June 2018 and December 2019. As a reference, the outcomes were compared with the Colombian registries on RES-Q platform. MATERIALS AND METHODS: A retrospective descriptive study of patients treated in-hospital with stroke, data collection was performed using the RES-Q platform. The analysis was carried out using descriptive statistics and absolute and relative frequencies and the differences with analytical tests. RESULTS: 457patients were evaluated, with ischemic stroke predominance, endovenous thrombolysis was performed in 7.2 % in 2018, and 9.2 % in 2019, 27.7 % of patients had door to needle time less than 60 minutes in 2018 and 42.8 % in 2019. Among the quality markers evaluated, an improvement was found in the performance of NIHSS, dysphagia evaluation, and carotid doppler performance in ischemic stroke. Compared with Colombian registry, a lower percentage was found in endovenous thrombolysis and thrombectomy. Most of Stroke Care Markers are similar to national average. CONCLUSIONS: The improvement in compliance of standard of Stroke Care Quality Markers reflects the impact of stroke care programs. The monitoring of quality parameters allows the generation of comprehensivestroke care programs in the region.

Whole-Genome Sequences of Two Campylobacter coli Isolates from the Antimicrobial Resistance Monitoring Program in Colombia.

Campylobacter coli, along with Campylobacter jejuni, is a major agent of gastroenteritis and acute enterocolitis in humans. We report the whole-genome sequences of two multidrug-resistance C. coli strains, isolated from the Colombian poultry chain. The isolates contain a variety of antimicrobial resistance genes for aminoglycosides, lincosamides, fluoroquinolones, and tetracycline.

Combinación del ácido úrico y albúmina sérica como biomarcadores predictivos de preeclampsia severa / Combination of uric acid and serum albumin as predictive biomarkers of severe preeclampsia

Resumen: OBJETIVO: Establecer si la la combinación de las concentraciones séricas de ácido úrico y albúmina en las semanas 20 a 24 del embarazo es predictora de preeclampsia severa. MATERIALES Y MÉTODOS: Estudio de casos y controles, retrospectivo y observacional, en el que se analizaron las concentraciones de ácido úrico y de albúmina coexistentes en las semanas 20 a 24; posteriormente se compararon las diferencias con pacientes con preeclampsia severa. Se recabaron los datos en Microsoft Excel para Mac versión 2019 y el análisis estadístico se realizó en SPSS para Mac versión 25. RESULTADOS: Se obtuvieron 122 casos y 199 controles. La elevación de las concentraciones de ácido úrico (≥ 4.9 mg/dL) y la hipoalbuminemia (menos de 3.5 mg/dL) tuvieron significación estadística para preeclampsia severa versus el grupo control (p < 0.001). El modelo de regresión logística obtuvo una razón de momios para predecir preeclampsia con datos de severidad de 6.736 (IC95%: 2.5-17.7) para la elevación del ácido úrico y razón de momios de 11.337 (IC95%: 4.5-28.3) para la hipoalbuminemia (p < 0.001). CONCLUSIÓN: El aumento en las concentraciones de ácido úrico (medidas entre las semanas 20 a 24 de embarazo) en combinación con la albúmina sérica tiene utilidad predictora de preeclampsia severa. Sin embargo, deben efectuarse más estudios clínicos para comprobar su eficacia y poder reducir la prevalencia de esta enfermedad.

Abstract: OBJECTIVE: To determine if the combination of serum uric acid and albumin levels from weeks 20 to 24 of gestation are predictors of severe preeclampsia. MATERIALS AND METHODS: A retrospective and observational case-control study was carried out, in which the levels of uric acid and albumin taken during the 20th to 24th week were analyzed and compared with patients who developed severe preeclampsia. The data was collected in Microsoft Excel for Mac version 2019 and the statistical analysis was performed in SPSS for Mac version 25. RESULTS: 122 cases and 199 controls were obtained. Elevation of uric acid levels (≥4.9 mg/dL) and hypoalbuminemia (<3.5 mg/dL) obtained statistical significance for severe preeclampsia compared to the control group (p <0.001). The logistic regression model obtained an OR to predict severe preeclampsia of 6.736 (CI95% 2.5-17.7) for uric acid elevation and OR of 11.337 (CI95% 4.5-28.3) for hypoalbuminemia (p <0.001). CONCLUSION: In this study the statistically significant relationship was observed between the increase in uric acid levels and serum hypoalbuminemia from weeks 20 to 24 as predictive biomarkers of severe preeclampsia. However, more studies should be carried out to verify its clinical utility.

Disfiguring disease, degeneration and climate in Colombia, 1880-1920.

This text aims to unite two neglected areas of study in Colombian medical historiography: disfiguring disease and the concept of climate. It seeks to show how physicians in the late nineteenth and early twentieth centuries in Colombia associate a clinical semiology of disfiguring disease with the influence of certain climatic and hereditary conditions. Characterizing disfiguring disease associated with climate implies revising the way in which, at the close of the nineteenth century, medical discourse constructed etiological explanations using the applied rationalism of the period. Thus, the ideal pathological terrain was both the body of the patient and the territory he or she inhabited.

Historia de la micología médica en Colombia, 1930-1970 / History of medical micology in Colombia, 1930-1970

El objetivo general de esta investigación fue comprender algunos de los acontecimientos históricos que posibilitaron la instauración, difusión y apropiación de la micología médica en Colombia entre 1930 y 1970. Para ello se consultaron revistas científicas y tesis en diferentes bibliotecas, centros documentales y archivos históricos de Medellín y de Bogotá. Se incluyen en el informe los diferentes problemas enfrentados por los médicos y el personal de laboratorio para la clasificación taxonómica de los hongos, la relación entre la micología y la dermatología, el desarrollo del estudio de las micosis sistémicas y el papel de algunas personas en la institucionalización de la micología médica.

The overall objective of this research was to understand the events that made possible the creation, diffusion and appropriation of medical mycology in Colombia between 1930 and 1970. It was based on the review of scientific journals and theses in different libraries, archives and documentation centers in Medellin and Bogota. The report includes the different problems faced by physicians and laboratory personnel concerning the classification of fungi, the relationship between dermatology and mycology, the development of the study of systemic mycoses and the role played by some persons in the institutionalization of medical mycology.

Enfermedad deformante, degeneración y clima en Colombia, 1880-1920 / Disfiguring disease, degeneration and climate in Colombia, 1880-1920

Este texto pretende unir dos objetos de estudio poco explorados en la historiografía médica colombiana: la enfermedad deformante y el concepto de clima. Busca poner de manifiesto cómo los médicos de finales del siglo XIX y comienzos del siglo XX en Colombia asocian una semiología clínica de las enfermedades deformantes con la influencia de ciertas condiciones climáticas y hereditarias. Caracterizar la enfermedad deformante asociada al clima, implica hacer una revisión de la manera cómo, al finalizar el siglo XIX, el discurso médico construyó explicaciones etiológicas propias del racionalismo aplicado en la época. De este modo, el terreno ideal patológico era tanto el cuerpo del paciente como el territorio habitado.

Factores no biológicos relacionados con el desarrollo de resistencia de Plasmodium falciparum a la cloroquina / Non-biological factors related to the development of resistance to chloroquine in Plasmodium falciparum

El desarrollo de resistencia de Plasmodium falciparum a los antimaláricos constituye unproblema importante para el control de la malaria. Particularmente, el surgimiento y dispersión de cepas de P. falciparum resistentes a la cloroquina a partir de la segunda mitad delsiglo XX representan un nuevo problema para su control. La literatura científica ha documentado factores relacionados con el hospedero humano, el vector, el parásito y el tratamiento que podríanexplicar la selección, supervivencia y dispersión local o a distancia de estas cepas. En esta revisión se exploraron factores no biológicos que intentan explicar el surgimiento y dispersión de cepas P. falciparum resistentes a la cloroquina. El entendimiento de los factores que contribuyen al surgimientode la resistencia a antimaláricos, es importante para el diseño de estrategias que busquen retardar la aparición de resistencia a nuevos antimaláricos.

The development of Plasmodium falciparum resistantto antimalarial drugs constitutes a major public health issue for malaria control. Particularly,the emergence and widespread of chloroquine resistant P. falciparum strains in the second half ofXX century represents a new challenge to malaria control. The scientific literature has documentedfactors related to the human host, the vector, the parasite and the treatment, which could explainthe selection, survival and local or wide spread of these strains. In this paper are reviewed non-biologicalfactors that could explain the emergencyof P. falciparum resistant chloroquine strains. The understanding of these factors is relevant to designstrategies to delay the emergence of antimalarial drug resistant parasites.