Role of the first WHO mutation catalogue in the diagnosis of antibiotic resistance in Mycobacterium tuberculosis in the Valencia Region, Spain: a retrospective genomic analysis.

BACKGROUND: In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting. METHODS: In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay. FINDINGS: WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8-94·4) for isoniazid, 73·3% (44·9-92·2) for rifampicin, 50·0% (21·1-78·9) for ethambutol, and 57·1% (34·0-78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected. INTERPRETATION: We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting. FUNDING: European Research Council and the Spanish Ministerio de Ciencia.

Incidence, Hospitalization, Mortality and Risk Factors of COVID-19 in Long-Term Care Residential Homes for Patients with Chronic Mental Illness.

Long-term care residential homes (LTCRH) for patients with chronic mental illness have suffered the enormous impact of COVID-19. This study aimed to estimate incidence, hospitalization, mortality, and risk factors of COVID-19 to prevent future epidemics. From March 2020 to January 2021 and before vaccination anti-SARS-CoV-2 begins, cumulate incidence rate (CIR), hospitalization rate (HR), mortality rate (MR), and risk factors of COVID-19 in the 11 LTCRH of two Health Departments of Castellon (Spain) were studied by epidemiological surveillance and an ecological design. Laboratory tests confirmed COVID-19 cases, and multilevel Poisson regression models were employed. All LTCRH participated and comprised 346 residents and 482 staff. Residents had a mean age of 47 years, 40% women, and suffered 75 cases of COVID-19 (CIR = 21.7%), five hospitalizations (HR = 1.4%), and two deaths (MR = 0.6%) with 2.5% fatality-case. Staff suffered 74 cases of the disease (CIR = 15.4%), one hospitalization (HR = 0.2%), and no deaths were reported. Risk factors associated with COVID-19 incidence in residents were private ownership, severe disability, residents be younger, CIR in municipalities where LTCRH was located, CIR in staff, and older age of the facilities. Conclusion: COVID-19 incidence could be prevented by improving infection control in residents and staff and modernizing facilities with increased public ownership.

Incidence, Mortality, and Risk Factors of COVID-19 in Nursing Homes.

During the period from March 2020 to January 2021, we performed an analysis of incidence, mortality, and risk factors of COVID-19 in nursing homes (NHs) in two health departments (HDs) of Castellon (Spain) 2021 through epidemiological surveillance and an ecological design. Laboratory-confirmed COVID-19 cases, cumulative incidence rate (CIR), and mortality rate (MR) of 27 NHs were collected. Information of residents, staff, and facilities was obtained by questionnaire. Multilevel Poisson regression models were applied. All NHs in the HDs participated with 2229 residents (median: 83 years old, 67.3% women) and 1666 staff. Among residents, 815 cases (CIR: 34.8 per 100) and 202 deaths (MR: 8.7 per 100, case fatality 21.0%) were reported and, among staff, 296 cases (CIR: 19.2 per 100) without deaths. Residents' CIR and MR increased with staff CIR, age of the building, residents/staff ratios, occupancy rate, and crowding index; CIR increased with private NH ownership, large NH size, large urban area, and the percentage of women residents; and MR was associated with residents' severe disabilities. In conclusion, several risk factors of COVID-19 incidence and mortality can be prevented by improving infection and quality controls, ameliorating residents/staff ratios, improving structural facilities, and increasing NH public ownership to avoid new outbreaks.

Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics.

Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.

[Comparison of postvaccinal antibodies to SARS-CoV-2 in asymptomatic cases, symptomatic cases, and non-cases in a cohort of general hospital workers]. / Comparación de anticuerpos postvacunales al SARS-CoV-2 en casos asintomáticos, casos sintomáticos, y no casos de una cohorte de trabajadores de un hospital general.

Estimada Sra. Directora: Agradecemos a los doctores Rujittika Mungmunpuntipantip y Viroj Wiwanitkit su interés por nuestra publicación(1) en la carta en la que se subrayan la importancia de los casos asintomáticos de COVID-19 en la evaluación de los efectos de la vacunación anti-SARS-CoV-2(2). Compartimos con ellos que las personas asintomáticas al COVID-19 pueden presentar unos niveles de anticuerpos anti-SARS-CoV-2 IgG-S mayores que las personas sin historia previa de COVID-19, y que pueden diferir en las reacciones a la vacunación, considerando que la prevalencia de COVID-19 asintomáticos se ha descrito como elevada(3).  En nuestra cohorte de trabajadores del Hospital General Universitario de Castellón, se detectaron 5 casos de COVID-19 asintomáticos (CA), incluyendo los dos seguimientos realizados(1,4), y 20 casos presentaron síntomas de COVID-19 (CS), con un total de 25 casos con confirmación por el laboratorio, 20 % tasa de asintomáticos (5/25). En la tabla 1 se recogen las características de los CA, CS, y de los participantes que no habían sufrido la enfermedad. Los CA eran más jóvenes que los otros 2 grupos, y la proporción de varones era significativamente mayor (p=0,027). En cuanto a los anticuerpos Anti-SARS-CoV-2 IgG-S al mes de la vacunación, los niveles de los CS fueron mayores que los de CA, y de los no casos, siendo estos últimos los que tuvieron significativamente menores niveles (p<0,001). Sin embargo, a los 8 meses de la vacunación la caída de IgG-S fue general, y los niveles de IgG-S eran mayores en los CA que en los CS y en los no casos (p<0,001). Los niveles de IgG-S considerados como protectores ? 4160 UA/ml, eran mayores en los CA y CS que el de los no casos (p=0,001). Si bien, el declive era similar en los tres grupos (p=0,084). Los síntomas y los efectos secundarios de las dos dosis de vacuna Pfizer-BioNTech no presentaron diferencias significativas entre los grupos. Estos resultados son coincidentes con númerosos estudios, en los que se constata que los casos de COVID-19 presentan niveles más elevados de IgG-S que las personas que no han sufrido la enfermedad(5), y se apreció que en valores medio no se alcanzaron los niveles de IgG-S protectores. De aquí la importancia de disponer de marcadores más efectivos de la situación de protección de la personas vacunadas tanto si han sufrido la enfermedad como sino. Además de los anticuerpos neutralizantes, la determinación de la inmunidad celular podría ser muy conveniente para conocer los niveles de protección.

Respuesta vacunal frente a SARS-CoV-2 en trabajadores de un hospital / Vaccine response to SARS-CoV-2 in hospital workers

Introducción: Evaluar la inmunidad de los trabajadores de un hospital tras haber completado la vacunación Pfizer-BionTech, y su relación con factores individuales. También describir los efectos adversos de la vacuna. Método: Estudio transversal de una muestra de los trabajadores del Hospital General Universitario de Castellón vacunados con dos dosis en enero y febrero de 2021. Un mes después se detectaron: anticuerpos IgG frente a la proteína N (IgG-NP), de IgM frente a la proteína S (IgM-S) y detección cuantitativa de IgG frente a la proteína S (IgG-Quant). Se utilizó un cuestionario para recoger datos demográficos, factores de riesgo y efectos secundarios. En el análisis estadístico se utilizaron modelos de regresión múltiple. Resultados: La participación fue del 96,8% (275/284). Presentaron IgG-Quant el 99,6%, 14,9% IgM-S, y 4,4% IgG-NP. El nivel ajustado de IgG-Quant aumentó significativamente con la obesidad, en no fumadores y con positividad IgM-S y/o IgG-NP. La prevalencia de IgM-S era mayor en varones, y se asociaba con los mismos factores que la IgG-Quant. De los infectados por COVID-19, el 42,9% no presentaron IgG-NP. Un 86,5% sufrió algún efecto secundario que se asoció a tener IgG-NP, mayores niveles de IgG-Quant, y fue más frecuente en jóvenes y mujeres. Conclusiones: Todos los participantes desarrollaron inmunidad humoral excepto uno. Tuvieron mayores niveles de anticuerpos los que habían padecido la COVID-19. Un porcentaje alto desarrolló efectos secundarios leves, más frecuentes en los que habían padecido la enfermedad (AU)

Introduction: The aim of this study was to measure anti-SARS-CoV-2 immunity of hospital workers after a completed 2-dose Pfizer-BionTech vaccination, and to examine factors potentially associated with immunity status. Side effects of the vaccine were also studied. Method: This was a cross-sectional study of a representative sample of General University Hospital of Castellon workers, vaccinated with two doses in January and February 2021. We measured IgG antibodies against protein N (IgG-NP), IgM against protein S (IgM-S), and quantitative levles of IgG against protein S (IgG-Quant) one month after the last dose. We obtained information on demographic, risk factors, and vaccine side effects via a self-completed questionnaire. For the statistical analysis we used multiple regression models. Results: Two hundred seventy-five workers participated (96.8%, 275/284). Positive IgG-Quant, IgM-S, and IgG-NP were 99.6%, 14.9% and 4.4%, respectively. Adjusted IgG-Quant levels increased significantly with obesity, nonsmoking status, positive IgM-S, and/or IgG-NP. The prevalence of IgM-S was higher in males, and associated with the same factors as those for IgG-Quant. Among those with a history of COVD-19 infection, 42.9% did not have IgG-NP. Overall 86.5% of participants had side effects, which were associated with positive IgG-NP, high IgG-Quant levels, younger age, and being female. Conclusions: All but one participant developed immunity. Those who had suffered from COVID-19 infection had higher antibody levels. A high proportion of participants had mild secondary effects, especially those with previous COVID-19 infection (AU)

[Vaccine response to SARS-CoV-2 in hospital workers]. / Respuesta vacunal frente a SARS-CoV-2 en trabajadores de un hospital.

INTRODUCTION: The aim of this study was to measure anti-SARS-CoV-2 immunity of hospital workers after a completed 2-dose Pfizer-BionTech vaccination, and to examine factors potentially associated with immunity status. Side effects of the vaccine were also studied. METHOD: This was a cross-sectional study of a representative sample of General University Hospital of Castellon workers, vaccinated with two doses in January and February 2021. We measured IgG antibodies against protein N (IgG-NP), IgM against protein S (IgM-S), and quantitative levles of IgG against protein S (IgG-Quant) one month after the last dose. We obtained information on demographic, risk factors, and vaccine side effects via a self-completed questionnaire. For the statistical analysis we used multiple regression models. RESULTS: Two hundred seventy-five workers participated (96.8%, 275/284). Positive IgG-Quant, IgM-S, and IgG-NP were 99.6%, 14.9% and 4.4%, respectively. Adjusted IgG-Quant levels increased significantly with obesity, nonsmoking status, positive IgM-S, and/or IgG-NP. The prevalence of IgM-S was higher in males, and associated with the same factors as those for IgG-Quant. Among those with a history of COVD-19 infection, 42.9% did not have IgG-NP. Overall 86.5% of participants had side effects, which were associated with positive IgG-NP, high IgG-Quant levels, younger age, and being female. CONCLUSIONS: All but one participant developed immunity. Those who had suffered from COVID-19 infection had higher antibody levels. A high proportion of participants had mild secondary effects, especially those with previous COVID-19 infection.

Introducción: Evaluar la inmunidad de los trabajadores de un hospital tras haber completado la vacunación Pfizer-BionTech, y su relación con factores individuales. También describir los efectos adversos de la vacuna. Método: Estudio transversal de una muestra de los trabajadores del Hospital General Universitario de Castellón vacunados con dos dosis en enero y febrero de 2021. Un mes después se detectaron: anticuerpos IgG frente a la proteína N (IgG-NP), de IgM frente a la proteína S (IgM-S) y detección cuantitativa de IgG frente a la proteína S (IgG-Quant). Se utilizó un cuestionario para recoger datos demográficos, factores de riesgo y efectos secundarios. En el análisis estadístico se utilizaron modelos de regresión múltiple. Resultados: La participación fue del 96,8% (275/284). Presentaron IgG-Quant el 99,6%, 14,9% IgM-S, y 4,4% IgG-NP. El nivel ajustado de IgG-Quant aumentó significativamente con la obesidad, en no fumadores y con positividad IgM-S y/o IgG-NP. La prevalencia de IgM-S era mayor en varones, y se asociaba con los mismos factores que la IgG-Quant. De los infectados por COVID-19, el 42,9% no presentaron IgG-NP. Un 86,5% sufrió algún efecto secundario que se asoció a tener IgG-NP, mayores niveles de IgG-Quant, y fue más frecuente en jóvenes y mujeres. Conclusiones: Todos los participantes desarrollaron inmunidad humoral excepto uno. Tuvieron mayores niveles de anticuerpos los que habían padecido la COVID-19. Un porcentaje alto desarrolló efectos secundarios leves, más frecuentes en los que habían padecido la enfermedad.

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant.

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain.

BACKGROUND: Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened. METHODS AND FINDINGS: We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02-1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region. CONCLUSIONS: In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.

Microbiota biliar en pacientes colecistectomizados: revisión de la antibioterapia empírica / Biliary microbiote in cholecystectomized PATIENTS: review of empirical antibiotherapy

INTRODUCCIÓN: La colecistitis constituye una importante causa de ingreso hospitalario. En colecistitis moderada o severa, el retraso en el tratamiento puede acarrear complicaciones graves. Nuestro objetivo es analizar los microorganismos aislados en bilis de pacientes colecistectomizados y su patrón de sensibilidad para evaluar el tratamiento empírico en aquellos casos en que la extirpación quirúrgica de la vesícula deba demorarse. PACIENTES Y MÉTODOS: Estudio descriptivo prospectivo de los cultivos biliares de pacientes sometidos a colecistectomía desde mayo de 2013 hasta febrero de 2015, en el Servicio de Cirugía del Hospital General Universitario de Castellón. RESULTADOS: Se estudiaron 196 pacientes, 83 mujeres (42,3%) y 113 hombres (57,7%), con una media de edad de 61,5 años. Los antibióticos más utilizados como tratamiento empírico fueron piperacilina/tazobactam (77,8%) y amoxicilina/clavulánico (14,8%). En el 46,4% de los pacientes (91/196) los cultivos de bilis fueron positivos. Se aislaron un total de 165 microorganismos. La mayoría eran bacilos gramnegativos (60,5%), principalmente Enterobacterales (91/54,5%), siendo Escherichia coli el microorganismo más frecuente (24%) seguido de Klebsiella spp. (12,5%). Se aislaron 3 E. coli productoras de betalactamasa de espectro extendido (BLEE) y 1 Klebsiella pneumoniae BLEE. No se aislaron microorganismos productores de carbapenemasa ni Staphylococcus aureus resistente a meticilina. CONCLUSIÓN: La microbiota biliar, con predominio de Enterobacterales, es similar a la encontrada en estudios europeos

INTRODUCTION: Cholecystitis is an important cause of hospital admission. In moderate or severe cholecystitis, the delay in treatment can lead to serious complications. Our objective is to analyze the microorganisms isolated in bile from cholecystectomized patients and their sensitivity pattern, to evaluate the empirical treatment in those cases in which the surgical removal of the gallbladder should be delayed. PATIENTS AND METHODS: Prospective descriptive study of biliary cultures of patients undergoing cholecystectomy from May 2013 to February 2015, in the Surgery Department of the Hospital General Universitari de Castelló. RESULTS: We studied 196 patients, 83 women (42.3%) and 113 men (57.7%), with an average age of 61.5 years. The most used antibiotics as empiric treatment were piperacillin/tazobactam (77.8%) and amoxicillin/clavulanic (14.8%). In 46.4% of patients (91/196) bile cultures were positive.165 microorganisms were isolated. The majority were Gram-negative bacilli (60.5%), mainly of the Enterobacterales order (91/54.5%), with Escherichia coli being the most frequent microorganism (24%) followed by Klebsiella spp. (12.5%).3 E. coli with extended-spectrum beta-lactamase (ESBL) and 1 K. pneumoniae with ESBL were isolated. Microorganisms producing carbapenemase and methicillin-resistant Staphylococcus aureus were not isolated. CONCLUSION: The bile microbiota, with a predominance of Enterobacterales is similar to that found in european studies

Pulmonary Versus Extrapulmonary Tuberculosis Associated Factors: A Case-Case Study.

BACKGROUND: Tuberculosis (TB) incidence remains low in health departments of Castellon and La Plana-Vila-real, but TB elimination is challenging. The objective of this study was to estimate associated factors of pulmonary tuberculosis (PTB) compared with extrapulmonary tuberculosis (ETB) and investigate epidemiological characteristics of these pathologies to orient control and prevention actions. MATERIALS AND METHODS: A prospective case-case study was implemented by comparing PTB and ETB incidences during 2013-2016 from notification reports, epidemiological surveillance, and microbiological results of hospitals' laboratories Hospital General Castellon and La Plana-Vila-Real in the province of Castellon of Valencia region in Spain. In this design, cases were patients with PTB and controls were patients with ETB. Directed acyclic graph approach was used for selection of potential risk and confounding factors. Adjusted odds ratios (AORs) were estimated by logistic regression models. RESULTS: The study included 136 patients with PTB and 57 patients with ETB, with microbiological confirmation of 93.4% and 52.6%, and the annual median of incidence rates were 7.5 and 3.1 per 100 000 inhabitants, respectively. In general, patients with PTB were younger with higher male proportion than patients with ETB. Risk factors of PTB were smoking tobacco (AOR = 3.98; 95% confidence interval [CI] = 1.66-9.56), social problems (social marginalization, homeless, residence in shelters for the poor, or stay in prison) (AOR = 3.39; 95% CI = 1.05-10.94), and contact with patients with TB (AOR = 2.51; 95% CI = 1.06-5.95). No-smoking tobacco and no-drug abuse interaction decrease PTB risk (AOR = 0.27; 95% CI = 0.12-0.64). From these results, specific measures of health promotion and prevention can be addressed. CONCLUSIONS: The estimated associated factors of PTB may be prevented, and it was demonstrated that the case-case design is useful in the study of TB.

Comparison of sporadic cases of Salmonella Typhimurium with other Salmonella serotypes in Castellon (Spain): case-case study / Comparación de casos esporádicos de Salmonella typhimurium con otros serotipos de Salmonella en Castellón (España): un estudio caso-caso

INTRODUCTION: Salmonella infections (SI) are common in Spain. The aim of this study was to appraise risk factors and the clinical characteristics of sporadic Salmonella Typhimurium infections compared with other sporadic salmonella serotype infections (OSI). METHODS: From September 2014 to August 2015, a case-case study was carried out by the Epidemiology Division of the Public Health Centre of Castellon. Case 1 consisted of patients with sporadic S. Typhimurium infections, while case 2 comprised OSI patients, assessed according to the stool cultures analyzed by the Microbiology Laboratories of Hospital General de Castellon and Hospital de La Plana in Vila-real. Patients from detected outbreaks were not included. The salmonella serotype was identified by the National Centre of Microbiology (Madrid). RESULTS: The total number of SI patients reported was 327, 242 of whom were studied (74.0%). 148 patients had sporadic S. Typhimurium infection and 64 had OSI, with median ages of 4 and 8.5 years, respectively. Sporadic S. Typhimurium infection patients presented more blood in feces and diarrhea episodes. Consumption of pork meat (OR = 2.22; 95% CI 1.12-4.43), cold pork meats (OR = 2.49; 95% CI 1.32-4.68) and playing in the dirt (OR=3.02; 95% CI 1.55-5.88), were associated with sporadic S. Typhimurium infection. In the 0-4 year-old group, the associated factors were consumption of cold pork meats, omelets and female gender. In the 5-year-old and over group, only playing in soil was associated with sporadic S. Typhimurium infection. CONCLUSIONS: The consumption of pork and omelets, as well as playing in the dirt, were the main factors associated with infection. Children were most affected by sporadic S. Typhimurium infection

INTRODUCCIÓN: Las infecciones por Salmonella son frecuentes en España. El objetivo de este estudio fue estimar factores de riesgo y características de las infecciones esporádicas por Salmonella typhimurium (IET), comparadas con infecciones esporádicas por otros serotipos de Salmonella. MÉTODOS: Desde septiembre de 2014 a agosto de 2015 se efectuó un estudio caso-caso por la Sección de Epidemiología del Centro de Salud Pública de Castellón. El caso 1 fueron los pacientes con IET y el caso 2 aquellos con infecciones esporádicas por otros serotipos de Samonella, según los coprocultivos realizados por los laboratorios de Microbiología de los hospitales General de Castellón y La Plana de Vila-real, sin incluir los pacientes de brotes detectados. El serotipo de Salmonella fue identificado en el Centro Nacional de Microbiología (Madrid). RESULTADOS: Se notificaron 327 pacientes con infección por Salmonella, de los que 242 fueron estudiados (74,0%). Ciento cuarenta y ocho pacientes tenían IET y 64, infecciones esporádicas por otros serotipos de Salmonella, con una mediana de edad de 4 y 8,5 años, respectivamente. Los pacientes IET presentaron más episodios diarreicos y sangre en las heces. El consumo de carne de cerdo (OR 2,22; IC 95% 1,12-4,43), fiambres de cerdo (OR 2,49; IC 95% 1,32-4,68) y jugar en la tierra (OR 3,02; IC 95% 1,55-5,88) fueron asociados con IET. En el grupo de 0-4 años, los factores asociados fueron consumo de fiambres de cerdo, tortillas y ser mujer. En el grupo de 5 y más años, solo jugar en la tierra fue asociado con IET. CONCLUSIONES: El consumo de productos porcinos y tortillas, así como jugar en la tierra fueron los factores asociados, y los niños, los más afectados

Comparison of sporadic cases of Salmonella Typhimurium with other Salmonella serotypes in Castellon (Spain): case-case study.

INTRODUCTION: Salmonella infections (SI) are common in Spain. The aim of this study was to appraise risk factors and the clinical characteristics of sporadic Salmonella Typhimurium infections compared with other sporadic salmonella serotype infections (OSI). METHODS: From September 2014 to August 2015, a case-case study was carried out by the Epidemiology Division of the Public Health Centre of Castellon. Case 1 consisted of patients with sporadic S. Typhimurium infections, while case 2 comprised OSI patients, assessed according to the stool cultures analyzed by the Microbiology Laboratories of Hospital General de Castellon and Hospital de La Plana in Vila-real. Patients from detected outbreaks were not included. The salmonella serotype was identified by the National Centre of Microbiology (Madrid). RESULTS: The total number of SI patients reported was 327, 242 of whom were studied (74.0%). 148 patients had sporadic S. Typhimurium infection and 64 had OSI, with median ages of 4 and 8.5 years, respectively. Sporadic S. Typhimurium infection patients presented more blood in feces and diarrhea episodes. Consumption of pork meat (OR=2.22; 95% CI 1.12-4.43), cold pork meats (OR=2.49; 95% CI 1.32-4.68) and playing in the dirt (OR=3.02; 95% CI 1.55-5.88), were associated with sporadic S. Typhimurium infection. In the 0-4 year-old group, the associated factors were consumption of cold pork meats, omelets and female gender. In the 5-year-old and over group, only playing in soil was associated with sporadic S. Typhimurium infection. CONCLUSIONS: The consumption of pork and omelets, as well as playing in the dirt, were the main factors associated with infection. Children were most affected by sporadic S. Typhimurium infection.

Influencia de la fase preanalítica en la cuantificación de la carga viral: aprendiendo de la experiencia / Influence of pre-analytical phase in viral load quantification: learning with the experience

No disponible

An outbreak of monophasic and biphasic SalmonellaTyphimurium, and Salmonella Derby associated with the consumption of dried pork sausage in Castellon (Spain) / Un brote de Salmonella Typhimurium monofásica y bifásica y Salmonella Derby asociado al consumo de longaniza seca de cerdo en Castellón (España)

An outbreak of S.Typhimurium occurred in several towns and cities in the province of Castellon (Spain) between 23 February and 27 May 2011. On April 5, the microbiology laboratory of a hospital in Castellon alerted the health authorities to the increase in S.Typhimurium isolated in fecal culture of children with gastroenteritis. The serotype and phage-type of 83 positive cases of S.Typhimurium isolated in these period included 49 monophasic/biphasic S.Typhimurium phage type 138, phage type 193, S.Derby, and 34 other S.Typhimurium phage-types. The median of age of patients was 4 years with a range of 0.6-80 years, and the 18% of patients were hospitalised. Two incident matched case-control studies were carried out; the first with S.Typhimurium phage type 138, 193, and S.Derby cases and the second with the other cases. The two studies found that the consumption of brand X dried pork sausage, purchased in a supermarket chain A, was associated with the disease (matched Odds Ratio [mOR]=13.74 95% Confidence Interval [CI] 4.84-39.06 and mOR=8.20 95% CI 2.32-28.89), respectively). S.Typhimurium phage type 193 and S.Derby were isolated in the food taken from the household of two patients and from the supermarket chain's A central warehouse. The pulsed-field gel electrophoresis study confirmed the similarity of the strains from the patients and the food. On May 25 2011, a national food alert led to the withdrawal of the food from the chain A and the outbreak ended

Entre el 23 de febrero y el 27 de mayo del 2011, un brote de Salmonella Typhimurium ocurrió en varios pueblos y ciudades en la provincia de Castellón (España). El día 5 de abril del 2011 el laboratorio de Microbiología de un hospital de Castellón alertó a las autoridades sanitarias del incremento de aislamientos de S.Typhimurium en coprocultivos de niños con gastroenteritis. El serotipo y fagotipo de 83 casos positivos a S.Typhimurium aislados en este periodo incluyó 49 casos con monofásica/bifásica S.Typhimurium fagotipo 138, fagotipo 193, y Salmonella Derby y otros 34 casos con distintos S.Typhimurium fagotipos. La mediana de los pacientes era de 4 años, con un rango de 0,6 a 80años. Dos incidentes casos-control apareados fueron llevados a cabo, el primero con los casos S.Typhimurium fagotipos 138,193 y S.Derby, y el segundo con los demás casos. Los 2 estudios encontraron que el consumo de la marca X de longaniza seca de cerdo comprada en una cadena de supermercados A estaba asociado con la enfermedad (odds ratio apareada [ORa]=13,74; intervalo de confianza [IC] del 95%: 4,84-39,06, y ORa=8,20; IC95%: 2,32-28,89, respectivamente). S.Typhimurium fagotipo 193 y S.Derby fueron aislados en dicho alimento recogido en la casa de 2 pacientes y en el almacén central de la cadena A de supermercados. La electroforesis en gel de campo pulsado confirmó la similitud de las cepas de los pacientes y del alimento. El día de 25 de mayo de 2011 una alerta alimentaria nacional obligó a la retirada del alimento de la cadena A y el brote terminó

An outbreak of monophasic and biphasic Salmonella Typhimurium, and Salmonella Derby associated with the consumption of dried pork sausage in Castellon (Spain).

An outbreak of S.Typhimurium occurred in several towns and cities in the province of Castellon (Spain) between 23 February and 27 May 2011. On April 5, the microbiology laboratory of a hospital in Castellon alerted the health authorities to the increase in S.Typhimurium isolated in fecal culture of children with gastroenteritis. The serotype and phage-type of 83 positive cases of S.Typhimurium isolated in these period included 49 monophasic/biphasic S.Typhimurium phage type 138, phage type 193, S.Derby, and 34 other S.Typhimurium phage-types. The median of age of patients was 4 years with a range of 0.6-80 years, and the 18% of patients were hospitalised. Two incident matched case-control studies were carried out; the first with S.Typhimurium phage type 138, 193, and S.Derby cases and the second with the other cases. The two studies found that the consumption of brand X dried pork sausage, purchased in a supermarket chain A, was associated with the disease (matched Odds Ratio [mOR]=13.74 95% Confidence Interval [CI] 4.84-39.06 and mOR=8.20 95% CI 2.32-28.89), respectively). S.Typhimurium phage type 193 and S.Derby were isolated in the food taken from the household of two patients and from the supermarket chain's A central warehouse. The pulsed-field gel electrophoresis study confirmed the similarity of the strains from the patients and the food. On May 25 2011, a national food alert led to the withdrawal of the food from the chain A and the outbreak ended.

Impacto de la inmigración desde Rumanía en la tuberculosis de un área mediterránea / No disponible

Fundamento: Conocer las características de la Tuberculosis en la provincia de Castellón y analizar los cambios que ha producido en ella la llegada de la inmigración procedente de Rumanía. Métodos: Estudio observacional retrospectivo de todos los casos declarados de Tuberculosis en los departamentos 2 y 3 de la Comunidad Valenciana entre los años 2004 y 2007.Resultados: Se estudiaron 306 casos, observando estabilización de casos en autóctonos y progresivo aumento en inmigrantes que en 2007 suponen el 47%, de los cuales el 64%procede de Rumanía. Los pacientes rumanos son más jóvenes (33,8 frente a 47,8 años), previamentesanos, con más proporción de mujeres (47% frente a 67%) y formas clínicas exclusivamente pleuropulmonares. Presentan elevado porcentaje de abandono de tratamiento (7,9%)y pérdidas del caso (15,8%). La tasa global de resistencias a tuberculostáticos en el total de casos ha sido del 4,5% y la de multirresistencia del 1,4%. Las resistencias en el grupo total de inmigrantes han sido del 5,15%: 1,6% en el grupo de inmigrantes rumanos y 11,4% en el grupo de inmigrantes de otras nacionalidades. Conclusiones: El fenómeno de la inmigración está modificando la dinámica de la Tuberculosis en Castellón. Se ha producido un freno en el declive de las tasas anuales de incidencia a expensas del aumento de casos en extranjeros, que en 2007 suponen el 47%, siendo en su mayoría de nacionalidad rumana (AU)

Aim: To know the characteristics of the Tuberculosis in the Castellón’s province and to analyze the changes that this has produced in because of the arrival of the immigration proceeding from Romania. Methods: Retrospective observacional study of all the declared cases of Tuberculosis in the department 2 and 3 of Castellón’s province between the year 2004 and 2007.Results: 306 cases were studied, observing stabilization of cases in autocthonous and progressive increase in immigrants who in 2007 represented 47 %, of which 64 % comes from Romania. The rumanian patients are younger (33,8 from to 47,8 years), previously healthy, with a higher women’s proportion (47% from 67%) and with clinical forms exclusively pleuropulmonars. They present a high percentage of treatment abandon (7,9%) and losses of the case(15,8%). The global rate of resistances to tuberculostáticos in the whole of cases has been 4,5%and of multirresistencia 1,4 %. In the complete group of immigrants, total resistance has been5,15%: 1,6% in the group of rumanian immigrants and 11,4% in the group of immigrants of other nationalities. Conclusions: The phenomenon of immigration is modifying the dynamics of Tuberculosis in Castellón. A brake has taken place in the decline of represented annual rates of TB mainly off the increase of cases in foreigners, who in 2007 suppose 47 %, being in the main of Rumanian nationality (AU)

[Pseudomonas aeruginosa: antimicrobial resistance in clinical isolates. Castellón 2004-2008]. / Pseudomonas aeruginosa: resistencia antimicrobiana en aislados clínicos. Castellón 2004-2008.

Retrospective study of antimicrobial susceptibility of 1.943 Pseudomonas aeruginosa clinical isolates to amikacin, tobramycin, gentamicin, ceftazidime, cefepime, meropenem, piperacillin-tazobactam and ciprofloxacin during a five year period. The percentage of resistance went from 2.07% to amikacin from 15.89% to ciprofloxacin. These percentages showed differences depending on the extra or intrahospital origin, departments and samples. Isolates from hospital patients were significantly more resistant than the ones from ambulatory patients (p < or = 0.001;tobramycin,13.74% vs 5.05%; gentamicin, 13.74% vs 8.26%; ceftazidime, 12.67% vs 4.24%; cefepime, 11.48% vs 7.07%; meropenem, 8.57% vs 2.06%), except for amikacin (1.98% vs 2.2%, p=0.74), piperacillin/ tazobactam (6.07% vs 4.55%, p=0.14) and ciprofloxacin (17.17% vs 13.97%, p=0.06).Critical care department and respiratory samples showed the highest resistance percentages while surgery department and invasive samples showed the lowest. Multidrug-resistance was found in 4.8% of the isolates. When comparing our data with those from our previous study (1992-2003), we observed a significant reduction in antibiotic resistance to amikacin (7.74% vs 2.07%, p<0.001), tobramycin (13.61% vs 10.26%, p<0.001), gentamicin (30.85% vs 14.73%, p<0,001), ceftazidime (14.63% vs 9,28%, p<0.001), cefepime (12.31% vs 9.71%, p=0.005), and meropenem (7.74% vs 2.07%, p=0.001); and there were no changes in resistance to piperacillin-tazobactam (4.26% vs 5.46%, p=0,06) and ciprofloxacin (16.02% vs 15.89%, p=0.89). In the last years, the susceptibility pattern of P. aeruginosa to antimicrobial agents has changed in our health district, and it is very different from the one described in national studies so it would be very important to monitor susceptibility of clinical isolates periodically.

Pseudomonas aeruginosa: resistencia antimicrobiana en aislados clínicos. Castellón 2004 - 2008 / Pseudomonas aeruginosa: antimicrobial resistance in clinical isolates. Castellón 2004 - 2008

Estudio retrospectivo de la resistencia de 1.943 aisladosclínicos de Pseudomonas aeruginosa a amikacina, tobramicina,gentamicina, ceftazidima, cefepima, meropenem, piperacilina-tazobactam y ciprofloxacino durante un periodo de 5años.La resistencia global osciló desde el 2,07% para amikacinaal 15,89% para ciprofloxacino con diferencias según la procedenciadel paciente, servicios y muestras: los aislamientos depacientes ingresados fueron significativamente más resistentesque los de los ambulatorios, (p≤0,001: tobramicina, 13,74%vs 5,05%; gentamicina, 13,74% vs 8,26%; ceftazidima, 12,67%vs 4,24%; cefepima, 11,48% vs 7,07%; meropenem, 8,57% vs2,06%), salvo para amikacina (1,98% vs 2,2%, p=0,74), piperacilina/tazobactam (6,07% vs 4,55%, p=0,14) y ciprofloxacino(17,17% vs 13,97%, p=0,06). Los servicios de críticos y lasmuestras respiratorias presentaron las tasas más altas de resistenciamientras que los servicios quirúrgicos y las muestras invasivaspresentaron la mejor sensibilidad. Un 4,8% de los aislamientosfueron multirresistentes.Comparado con nuestro anterior estudio (1.992-2.003)observamos un descenso significativo de resistencia a amikacina(7,74% vs 2,07%, p<0,001), tobramicina (13,61% vs10,26%, p<0,001), gentamicina (30,85% vs 14,73%, p<0,001)ceftazidima (14,63% vs 9,28%, p<0,001), cefepima (12,31% vs9,71%, p=0,005) y meropenem (8,84% vs 5,96%, p=0,001) y semantienen piperacilina/tazobactam (4,26% vs 5,46%, p=0,06)y ciprofloxacino (16,02% vs 15,89%, p=0,89).En nuestra zona se ha producido en los últimos años uncambio en los patrones de susceptibilidad de P. aeruginosa,alejado del descrito a nivel nacional, lo que incide en la importanciadel seguimiento local periódico de la susceptibilidad delos aislados clínicos(AU)

Retrospective study of antimicrobial susceptibility of1.943 Pseudomonas aeruginosa clinical isolates to amikacin,tobramycin, gentamicin, ceftazidime, cefepime,meropenem, piperacillin-tazobactam and ciprofloxacinduring a five year period.The percentage of resistance went from 2.07% toamikacin from 15.89% to ciprofloxacin. These percentagesshowed differences depending on the extra or intrahospitalaryorigin, departments and samples. Isolatesfrom hospital patients were significantly more resistantthan the ones from ambulatory patients (p≤0.001:tobramycin,13.74% vs 5.05%; gentamicin, 13.74% vs8.26%; ceftazidime, 12.67% vs 4.24%; cefepime, 11.48%vs 7.07%; meropenem, 8.57% vs 2.06%),except for amikacin(1.98% vs 2.2%, p=0.74), piperacillin/tazobactam(6.07% vs 4.55%, p=0.14) and ciprofloxacin (17.17% vs13.97%, p=0.06). Critical care department and respiratorysamples showed the highest resistance percentageswhile surgery department and invasive samples showedthe lowest. Multidrug-resistance was found in 4.8% ofthe isolates.When comparing our data with those from our previousstudy (1992-2003), we observed a significant reductionin antibiotic resistance to amikacin (7.74% vs2.07%, p<0.001), tobramycin (13.61% vs 10.26%,p<0.001), gentamicin (30,85% vs 14.73%, p<0,001), ceftazidime(14.63% vs 9,28%, p<0.001), cefepime (12,31%vs 9.71%, p=0.005), and meropenem (7.74% vs 2.07%,p=0.001); and there were no changes in resistance to piperacillin-tazobactam (4.26% vs 5.46%, p=0,06) and ciprofloxacin (16.02% vs 15.89%, p=0.89).In the last years, the susceptibility pattern of P. aeruginosato antimicrobial agents has changed in our healthdistrict, and it is very different from the one describedin national studies so it would be very important tomonitore susceptibility of clinical isolates periodically(AU)