Caracterización fenotípica y genotípica de aislamientos colombianos de Neisseria gonorrhoeae, recuperados a través del programa nacional de vigilancia por laboratorio, 2013-2014

La gonorrea es una enfermedad de transmisión sexual la cual es ocasionada por la bacteria Neisseria gonorrhoeae. Esta infección representa un problema serio de salud pública global, debido la aparición, incremento y dispersión de cepas con resistencia a los antimicrobianos. Adicionalmente, existen otras problemáticas asociadas, como la falta de síntomas en algunas mujeres, el desconocimiento de la enfermedad, el tratamiento sindromico, y el sub-registro. En Colombia, el Instituto Nacional de Salud (INS) desarrolla desde el año 1983 un programa de vigilancia voluntaria por laboratorio de N. gonorrhoeae, en base a esto se realizó el presente estudio, con el objetivo de caracterizar fenotípica y genotípicamente los aislamientos de N. gonorrhoeae, enviados al INS por los Laboratorios de Salud Pública (LSP) durante el periodo 2013-2014. Los aislamientos reportados durante el periodo de estudio, se recibieron de 19 entidades de salud del país, los cuales fueron confirmados mediante las pruebas fenotípicas, se determinó la sensibilidad antimicrobiana de acuerdo a los parámetros del Clinical Laboratory Standards Institute CLSI y la caracterización genotípica se realizó mediante las técnicas de electroforesis en gel de campo pulsado (PFGE), Ng MAST y PCR para la identificación del gen TEM. Se recibieron 246 aislamientos, pero solo fue posible aislar y confirmar la bacteria en 126 (58,53 %). Estos aislamientos provenían de Bogotá 62 (25,2 %), Antioquia 54 (21,9 %), Amazonas 47 (19,1 %) y Risaralda 33 (13,4 %). De los aislamientos recibidos, 188 (76,42 %) eran de hombres, 58 (23,57 %) de mujeres, 50 (20,33 %) eran de menores de 15 años, de los cuales 37 (63,79 %) se aislaron en niñas. La resistencia a penicilina, tetraciclina y ciprofloxacina fue de 65,8 %, 42,8 % y 29,4 %, respectivamente. La multirresistencia se presentó en 14 (11,11 %) aislamientos. Se encontraron 13 fenotipos de resistencia de los cuales el más común fue N. gonorrhoeae productora de penicilinasa (PPNG) (34/126; 26.98%). La PFGE agrupó 110 aislamientos en 17 grupos, con 54 patrones diferentes; los 16 aislamientos restantes no relacionaron genéticamente. El grupo más común fue el A, con 19 (15,1 %) aislamientos, la mayor parte de estos presentaron el fenotipo de resistencia PPNG. La prueba de Ng-MAST reveló una gran diversidad en los 20 aislamientos secuenciados debido a que no se encontró ninguna secuencia tipo (ST) predominante. En conclusión, los hallazgos del estudio sirven de línea base para el conocimiento de los aislamientos de N. gonorrhoeae que circulan en nuestro país. La resistencia y la gran variabilidad de las cepas reflejan que enfrentamos un preocupante problema de salud pública, que requiere una estrategia multidisciplinaria que incluya educación, campañas de prevención y promoción, mejora en los métodos diagnósticos y determinación de los perfiles de sensibilidad antimicrobiana.Abstract. Gonorrhoea is a sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae, this is a serious global public health problem, given increase in antimicrobial resistance. Asymptomatic women, ignorance of the disease, syndromic treatment and sub-register are additional problems to the disease. In Colombia, the National Health Institute (INS, in Spanish) has developed, since 1983, a program for laboratory surveillance of N. gonorrhoea with the voluntary participation of Public Health Laboratories (PHL) at the national level. The present study was conducted with the aim of characterizing phenotypically and genotypically the total number of N. gonorrhoeae isolates, received by the INS from PHL during the time period 2013-2014. The isolates reported during the period of study were received from 19 PHL. For phenotypic typification, assays of antimicrobial susceptibility according to the parameters of the CLSI were performed. Genotypic characterization achieved through techniques such as Electrophoresis Pulsed Field Gel (PFGE), Multi-antigen sequence typing (NG-MAST) and TEM- gene amplification. Out of a total of 246 isolates, we were able to identify the bacteria in 126 (58.53 %) cases. These isolates originated from Bogotá: 62 (25.2 %), Antioquia: 54 (21.9 %), Amazonas: 47 (19.1 %) and Risaralda: 33 (13.4 %). 188 (76.42 %) isolates were from men and 58 (23.57%) from women; 50 (20.33%) of them corresponded to children under 15 years of age and from these, 37 (63.79%) were female. We found 65.8 % resistance to penicillin, 42.8 % to tetracycline, and 29.4% to ciprofloxacin. Multi-resistance occurred in 14 (11.11%) isolates, 13 showed resistance phenotypes, and the most common was penicillinase producing N. gonorrhoeae (PPNG) found in 34 (26.98%) isolates. The PFGE grouped 110 isolates in 17 clusters, with 54 different patterns, while 16 isolates were unrelated. The most common cluster was A with 19 (15.1%) isolates; most of these showed the PPNG resistance phenotype. Ng-MAST (Multi Antigen Sequence Typing) revealed a high genetic diversity in the 20 isolates sequenced as not predominant sequence type was found. In conclusion, our findings serve as baseline for understanding N. gonorrhoeae isolates circulating in Colombia. Resistance and the high variability of strains represent serious public health problem, which requires a multidisciplinary strategy integrating education, prevention campaigns, improved diagnostic methods and determination of antimicrobial susceptibility profiles.Maestrí

Susceptibilidad de aislamientos de Neisseria gonorrhoeae a la penicilina y a la tetraciclina

A surveillance program of the antimicrobial susceptibility was established to determine antimicrobial resistance to Neisseria gonorrhoeae. We used the Kirby Bauer test to show that 42 out of 43 N. gonorrhoeae isolates of non beta lactamase producers (NBLP) presented an intermediate susceptibility level to penicillin. 26 of the same isolates were resistant to tetracycline. The minimal inhibitory concentration (MIC) to the two antimicrobials was determined in the 100 N. gonorrhoeae isolates from an STD program. From these 100 isolates, 49 were NPBL and 51 were PBL. MIC's to penicillin from the isolates PBL were interpreted as sensitive (2pg/mL) in 5. MIC's to penicillin from the isolates PBL showed that 4 were intermediate and 47 resistant. MIC's to tetracycline showed 4 isolates sensitive (2pglmL). This study indicated the need for surveillance programs for management of antimicrobial susceptibility of N. gonorrhoeae and treatment schedules.La vigilancia de la susceptibilidad antimicrobiana de los aislamientos de Neisseria qonorrhoeae es necesaria, debido a la capacidad de este patógeno para desarrollar resistencia por varios mecanismos, con las consecuentes fallas en el tratamiento. En un trabajo anterior, realizado en el Laboratorio de Microbiología del lnstituto Nacional de Salud, en el que se empleó la prueba de difusión de disco (Kirby-Bauer), se determinó en 43 aislamientos de N. gonorrhoeae no productores de beta-lactamasa, susceptibilidad intermedia a la penicilina en 42 y resistencia a la tetraciclina en 26. Por tal razón, se decidió establecer en todos los aislamientos de N. gonorrhoeae, remitidos al INS como parte del programa de red de ETS bacterianas, los niveles de resistencia a la penicilina y a la tetraciclina, expresados como la concentración inhibitoria mínima (CIM). De 100 aislamientos estudiados, 49 fueron no productores de beta-lactamasa (NPBL) y 51 productores (PBL). La CIM de la penicilina de los aislamientos NPBL fue menor o igual a 0,06 pg/mL (sensible) en 3; de 0,12-1 pg/mL (intermedia) en 41; y mayor o igual a 2 pg/mL en 5. La CIM de los aislamientos PBL señaló que 4 eran intermedios y 47 resistentes. La CIM de la tetraciclina fue menor o igual a 0,25 pg/mL (sensible) en 4, de 0,5 a pg/mL (intermedia) en 18 y mayor o igual a 2 pg/mL (resistente) en 78. Los datos destacan la importancia de mantener la vigilancia de la resistencia de N. gonorrhoeae a estos antimicrobianos para que, con base en ellos, se replanteen los esquemas de tratamiento

Streptococcus pneumoniae: evolución de los serotipos y los patrones de susceptibilidad antimicrobiana en aislamientos invasores en 11 años de vigilancia en colombia (1994 -2004).

Background. Streptococcus pneumoniae is an important cause of morbidity and mortality in children and adults in the world.Objective. Analysis of data from laboratory surveillance of S. pneumoniae, invasive isolates recovered from 1994 to 2004.Materials And Methods. Database of invasive isolates of S. pneumoniae, sent to the Microbiology Group through the national surveillance laboratory network of acute bacterial meningitis and acute respiratory infections, from 1994 to 2004. The isolates had epidemiological data, serotyping, antimicrobial susceptibility patterns and some of them molecular typing.Results. The data of 2,022 isolates from 120 hospitals of different regions of the country were analyzed. The isolates were recovered mainly from blood cultures (50.7%) and cerebrospinal fluid (42%). The most important serotypes were 14, 6B, 23F, 1, 5, 6A, 19F, 18C y 9V, which account for 83.6% of isolates obtained from children under 6 years of age, 74% from the 6 -14 year age group and 61.4% from children over 14 years of age. Overall, 29.8% of isolates presented diminished susceptibility to penicillin (DSP), 44.3% to trimethoprim-sulphamethoxazole, 32.4% to tetracycline, 8.2% to chloramphenicol and 3.8% to erythromycin. All isolates were susceptible to vancomycin and 13% were multiresistant. Six hundred two DSP isolates were molecularly typed, 27 (4.5%), were related with the Spain23F-1 clone, 38 (6.3%) with the Spain6B-2, 301 (50%) with the Spain9V-3 and 75 (12.5%) with the Colombia23F-26 clone. Moreover, all 138 isolates with capsular type 5 were related to the Colombia5-19 clone.Conclusion. The results provide basic information necessary to design and implement strategies for prevention of pneumococcal disease.Introducción. Streptococcus pneumoniae es una las principales causas de morbilidad y mortalidad en niños y adultos en el mundo. Objetivo. Realizar un análisis de los datos de la vigilancia por el laboratorio de los aislamientos invasores de S. pneumoniae recuperados entre 1994 y 2004. Materiales y métodos. Se empleó la información de los aislamientos invasores de S. pneumoniae recibidos en el Grupo de Microbiología del Instituto Nacional de Salud durante la vigilancia de meningitis bacteriana aguda e infección respiratoria aguda entre 1994 y 2004. Los aislamientos contaban con datos epidemiológicos, serotipo, patrones de susceptibilidad antimicrobiana y algunos con tipificación molecular. Resultados. Se analizaron los datos de 2.022 aislamientos procedentes de 120 hospitales de diferentes regiones del país, recuperados principalmente de hemocultivos (50,7%) y líquido cefalorraquídeo (42%). Los serotipos más importantes fueron el 14, 6B, 23F, 1, 5, 6A, 19F, 18C y 9V, los cuales corresponden al 83,6% en niños menores de 6 años, al 74,0% en el grupo de 6 a 14 años y al 61,4% en mayores de 14 años. El 29,8% de los aislamientos presentó susceptibilidad disminuida a la penicilina (SDP), 44,3% a trimetoprim-sulfametoxazol, 32,4% a tetraciclina, 8,2% a cloranfenicol, 3,8% a eritromicina; todos fueron sensibles a vancomicina y el 13% fue multirresistente. Se tipificaron 602 aislamientos con SDP, de los cuales 27 (4,5%) se relacionaron con el clon 1-España23F, 38 (6,3%) con el clon 2-España6B, 301 (50%) con el 3- España9V y 75 (12,5%) con el clon 26-Colombia23F, además, los 138 aislamientos con tipo capsular 5 se relacionaron con el clon 19-Colombia5. Conclusiones. Los resultados proporcionan información básica necesaria para el diseño e implementación de estrategias para la prevención de la enfermedad neumocócica en nuestro país

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis