Epidemic Diffusion Network of Spain: A Mobility Model to Characterize the Transmission Routes of Disease.

Human mobility drives the geographical diffusion of infectious diseases at different scales, but few studies focus on mobility itself. Using publicly available data from Spain, we define a Mobility Matrix that captures constant flows between provinces by using a distance-like measure of effective distance to build a network model with the 52 provinces and 135 relevant edges. Madrid, Valladolid and Araba/Álaba are the most relevant nodes in terms of degree and strength. The shortest routes (most likely path between two points) between all provinces are calculated. A total of 7 mobility communities were found with a modularity of 63%, and a relationship was established with a cumulative incidence of COVID-19 in 14 days (CI14) during the study period. In conclusion, mobility patterns in Spain are governed by a small number of high-flow connections that remain constant in time and seem unaffected by seasonality or restrictions. Most of the travels happen within communities that do not completely represent political borders, and a wave-like spreading pattern with occasional long-distance jumps (small-world properties) can be identified. This information can be incorporated into preparedness and response plans targeting locations that are at risk of contagion preventively, underscoring the importance of coordination between administrations when addressing health emergencies.

Epidemiological Characteristics and Spatio-Temporal Distribution of Hepatitis A in Spain in the Context of the 2016/2017 European Outbreak.

The aim of our study was to describe the results of the epidemiological surveillance of hepatitis A infections in Spain in the context of the 2016/2017 European outbreak, particularly of hepatitis A outbreaks reported in the MSM population, incorporating the results of a spatio-temporal analysis of cases. Hepatitis A cases and outbreaks reported in 2016-2017 to the National Epidemiological Surveillance Network were reviewed: outbreaks in which some of the cases belonged to the MSM group were described, and clusters of hepatitis A cases in men and women were analysed using a space-time scan statistic. Twenty-six outbreaks were identified, with a median size of two cases per outbreak, with most of the outbreak-related cases belonging to the 15-44 years-old group. Nearly 85% occurred in a household setting, and in all outbreaks, the mode of transmission was direct person-to-person contact. Regarding space-time analysis, twenty statistically significant clusters were identified in the male population and eight in the female population; clusters in men presented a higher number of observed cases and affected municipalities, as well as a higher percentage of municipalities classified as large urban areas. The elevated number of cases detected in clusters of men indicates that the number of MSM-related outbreaks may be higher than reported, showing that spatio-temporal analysis is a complementary, useful tool which may improve the detection of outbreaks in settings where epidemiological investigation may be more challenging.

Assessing the effect of non-pharmaceutical interventions on COVID-19 transmission in Spain, 30 August 2020 to 31 January 2021.

BackgroundAfter a national lockdown during the first wave of the COVID-19 pandemic in Spain, regional governments implemented different non-pharmaceutical interventions (NPIs) during the second wave.AimTo analyse which implemented NPIs significantly impacted effective reproduction number (Rt) in seven Spanish provinces during 30 August 2020-31 January 2021.MethodsWe coded each NPI and levels of stringency with a 'severity index' (SI) and computed a global SI (mean of SIs per six included interventions). We performed a Bayesian change point analysis on the Rt curve of each province to identify possible associations with global SI variations. We fitted and compared several generalised additive models using multimodel inference, to quantify the statistical effect on Rt of the global SI (stringency) and the individual SIs (separate effect of NPIs).ResultsThe global SI had a significant lowering effect on the Rt (mean: 0.16 ± 0.05 units for full stringency). Mandatory closing times for non-essential businesses, limited gatherings, and restricted outdoors seating capacities (negative) as well as curfews (positive) were the only NPIs with a significant effect. Regional mobility restrictions and limited indoors seating capacity showed no effect. Our results were consistent with a 1- to 3-week-delayed Rt as a response variable.ConclusionWhile response measures implemented during the second COVID-19 wave contributed substantially to a decreased reproduction number, the effectiveness of measures varied considerably. Our findings should be considered for future interventions, as social and economic consequences could be minimised by considering only measures proven effective.

Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019.

BACKGROUND: Botulism is a low incidence but potentially fatal infectious disease caused by neurotoxins produced mainly by Clostridium botulinum. There are different routes of acquisition, food-borne and infant/intestinal being the most frequent presentation, and antitoxin is the treatment of choice in all cases. In Spain, botulism is under surveillance, and case reporting is mandatory. METHODS: This retrospective study attempts to provide a more complete picture of the epidemiology of botulism in Spain from 1997 to 2019 and an assessment of the treatment, including the relationship between a delay in antitoxin administration and the length of hospitalization using the Cox proportional hazards test and Kruskal-Wallis test, and an approach to the frequency of adverse events, issues for which no previous national data have been published. RESULTS: Eight of the 44 outbreaks were associated with contaminated commercial foods involving ≤7 cases/outbreak; preserved vegetables were the main source of infection, followed by fish products; early antitoxin administration significantly reduces the hospital stay, and adverse reactions to the antitoxin affect around 3% of treated cases.

Hepatitis A Outbreak Characteristics: A Comparison of Regions with Different Vaccination Strategies, Spain 2010-2018.

We compared the cumulative incidence and characteristics of hepatitis A outbreaks in two groups of Spanish autonomous regions according to whether a universal or risk group vaccination strategy was followed. Outbreaks between 2010 and 2018 were analyzed. The cumulative incidence rate of outbreaks was estimated and compared by estimating the rate ratio (RR). The characteristics of the outbreaks and those of the first cases were compared. Adjusted OR (aOR) were calculated using a multivariate logistic regression model. Outbreak incidence was 16.04 per million persons in regions with universal vaccination and 20.76 in those with risk-group vaccination (RR 0.77; 95%CI 0.62-0.94). Imported outbreaks accounted for 65% in regions with universal vaccination and 28.7% in regions with risk-group vaccination (aOR 3.88; 95%CI 2.13-7.09). Adolescents and young adults aged 15-44 years and men who have sex with men were less frequently the first case of the outbreak in regions with a universal vaccination strategy (aOR 0.54; 95%CI 0.32-0.92 and 0.23; 95%CI 0.07-0.82, respectively). The cumulative incidence rate of outbreaks was lower in regions with universal vaccination. In all regions, independently of the vaccination strategy, activities to vaccinate persons belonging to high-risk groups for infection should be emphasized.

Real time surveillance of COVID-19 space and time clusters during the summer 2020 in Spain.

BACKGROUND: On June 21st de-escalation measures and state-of-alarm ended in Spain after the COVID-19 first wave. New surveillance and control strategy was set up to detect emerging outbreaks. AIM: To detect and describe the evolution of COVID-19 clusters and cases during the 2020 summer in Spain. METHODS: A near-real time surveillance system to detect active clusters of COVID-19 was developed based on Kulldorf's prospective space-time scan statistic (STSS) to detect daily emerging active clusters. RESULTS: Analyses were performed daily during the summer 2020 (June 21st - August 31st) in Spain, showing an increase of active clusters and municipalities affected. Spread happened in the study period from a few, low-cases, regional-located clusters in June to a nationwide distribution of bigger clusters encompassing a higher average number of municipalities and total cases by end-August. CONCLUSION: STSS-based surveillance of COVID-19 can be of utility in a low-incidence scenario to help tackle emerging outbreaks that could potentially drive a widespread transmission. If that happens, spatial trends and disease distribution can be followed with this method. Finally, cluster aggregation in space and time, as observed in our results, could suggest the occurrence of community transmission.

Fungal infections following treatment with monoclonal antibodies and other immunomodulatory therapies / Infecciones fúngicas como consecuencia de tratamientos con anticuerpos monoclonales y otras terapias inmunomoduladoras

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease

El factor de necrosis tumoral (TNF) es una citocina proinflamatoria involucrada en una amplia gama de procesos fisiológicos importantes y desarrolla un papel en la patogenia de algunas enfermedades. Los antagonistas del TNF (infliximab, adalimumab, etanercept) son efectivos en el tratamiento de afecciones inflamatorias. Los agentes biológicos antilinfocitarios (rituximab, alemtuzumab), los antagonistas de la integrina (natalizumab, etrolizumab y vedolizumab), de la interleucina 17A (secukinumab, ixekizumab) o los antagonistas de la IL-2 (daclizumab, basiliximab) se usan ampliamente después del trasplante y en trastornos gastroenterológicos, reumatológicos, dermatológicos, neurológicos y hematológicos. Dado el papel relevante de estos elementos de defensa del huésped contra agentes bacterianos, virales y fúngicos, el riesgo de infección durante el tratamiento con estos antagonistas genera preocupación. Las infecciones por hongos, tanto oportunistas como endémicos, se han asociado con estas terapias biológicas, pero la relación causal no está clara, especialmente entre los pacientes con un control deficiente de su enfermedad subyacente o que están recibiendo terapia con esteroides. Los pacientes en tratamiento con estos medicamentos deben ser examinados para detectar infecciones micóticas endémicas latentes. La profilaxis con cotrimoxazol podría ser útil para prevenir la infección por Pneumocystis jirovecii en pacientes mayores de 65 años que estén tomando antagonistas de TNF, agentes biológicos antilinfocitarios, o tengan linfopenia y estén en tratamiento concomitante con esteroides. Al igual que con otros fármacos inmunosupresores, deben suspenderse los antagonistas de TNF y los anticuerpos antilinfocitarios en pacientes con enfermedad infecciosa activa hasta su control

Fungal infections following treatment with monoclonal antibodies and other immunomodulatory therapies.

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease.

Indicator opportunistic infections after biological treatment in rheumatoid arthritis, 10 years follow-up in a real-world setting.

BACKGROUND: This research describes the incidence and factors associated with opportunistic infections in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: A retrospective longitudinal study was carried out from 2007 to 2018. We included RA patients treated with a tumor necrosis factor (TNF)-targeted bDMARD or non-TNF-targeted bDMARD from the start of bDMARDs. An independent variable was the development of an indicator of opportunistic infection after biological (IOIb) treatment. Secondary variables included sociodemographic, clinical, and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-years (95% CI). We performed a Cox multivariate regression analysis model to compare the risk of IOIb. Results were expressed as a hazard ratio (HR). RESULTS: A total of 441 RA patients were included, that started 761 different courses of bDMARDs. A total of 81% were women with a mean age at first bDMARD of 57.3 ±â€„14 years. A total of 71.3% of the courses were TNF-targeted bDMARDs and 28.7% were non-TNF-targeted bDMARDs. There were 37 IOIb (25 viral, 6 fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization and one died. The global incidence of IOIb was 23.2 (16.8-32). TNF-targeted bDMARDs had 25 IOIb, incidence 20.5 (13.9-30.4), and non-TNF-targeted bDMARDs had 12 IOIb, incidence 31.7 (18-55.9). In the multivariate analysis, glucocorticosteroids (HR 2.17, p = 0.004) and lower lymphocyte count increased the risk for IOIb (HR 0.99, p = 0.005). CONCLUSIONS: The incidence of IOIb due to bDMARDs was 23 cases per 1000 patient-years. Close monitoring should be taken in the RA patients treated with bDMARDs and glucocorticosteroids, mainly in elderly patients and those with a low total lymphocyte count at the beginning of bDMARD treatment.

Highlights in ASM MICROBE 2017 (New Orleans)

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Update in Infectious Diseases 2017 / Actualización en patología infecciosa 2017

Antimicrobial resistance in complex models of continuous infection is a current issue. The update 2017 course addresses about microbiological, epidemiological and clinical aspects useful for a current approach to infectious disease. During the last year, nosocomial pneumonia approach guides, recommendations for management of yeast and filamentous fungal infections, review papers on the empirical approach to peritonitis and extensive guidelines on stewardship have been published. HIV infection is being treated before and more intensively. The implementation of molecular biology, spectrometry and inmunology to traditional techniques of staining and culture achieve a better and faster microbiological diagnosis. Finally, the infection is increasingly integrated, assessing non-antibiotic aspects in the treatment (AU)

La resistencia a los antimicrobianos en modelos cada vez más complejos de infección continúa siendo actualidad. El curso de actualización de este año 2017 trata aspectos microbiológicos, epidemiológicos y clínicos útiles para un abordaje actual de la patología infecciosa. Durante el último año se han publicado guías de aproximación a la neumonía nosocomial, recomendaciones sobre el manejo de la infección fúngica por levaduras y filamentosos, documentos de revisión sobre el abordaje empírico de la peritonitis y una extensas guías sobre stewardship. En la infección por el VIH, cada vez se trata antes y más intensamente. La implementación de la biología molecular, la espectrometría y la inmunología a las técnicas tradicionales de tinción y cultivo consiguen un diagnóstico microbiológico mejor y más rápido. Por último, la infección se aborda de forma cada vez más integral, valorando aspectos no antibióticos en el tratamiento (AU)

Delafloxacin: design, development and potential place in therapy.

Delafloxacin (DLX) is a new fluoroquinolone pending approval, which has shown a good in vitro and in vivo activity against major pathogens associated with skin and soft tissue infections and community-acquired respiratory tract infections. DLX also shows good activity against a broad spectrum of microorganisms, including those resistant to other fluoroquinolones, as methicillin-resistant Staphylococcus aureus. Its pharmacokinetic properties and excellent activity in acidic environments make DLX an alternative in the treatment of these and other infections. In this manuscript, a detailed analysis of this new fluoroquinolone is performed, from its chemical structure to its in vivo activity in recently published clinical trials. Its possible place in the current antimicrobial outlook and in other infectious models is also discussed.

Controles interlaboratorio: algo más que un examen de conocimientos / Interlaboratory controls: more than just a knowledge test

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Activity of linezolid and tedizolid against clinical isolates of methicillin-resistant and methicillin and linezolid resistant Staphylococcus aureus: an in vitro comparison / Actividad comparativa in vitro entre linezolid y tedizolid frente a aislados clínicos de Staphylococcus aureus resistentes a meticilina y aislados resistentes también a linezolid

Introduction. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Spain is approximately 20- 30%. However, resistance to linezolid is rare, and the main reports are from nosocomial outbreaks. The objective of the present study was to compare the in vitro susceptibility of linezolid with that of tedizolid against MRSA isolates and methicillin- and linezolid-resistant isolates (MLRSA) mediated by the cfr gene. Material and methods. The in vitro susceptibility of linezolid and tedizolid was determined using the E-test with 18 MRSA strains and 18 cfr-mediated MLRSA strains obtained from clinical isolates in the microbiology service of a tertiary university hospital. Results. All MRSA strains were susceptible to both antibiotics. Analysis of the MRSA isolates revealed that the MIC50 and MIC90 of linezolid were 1.5 and 2 mg/L, respectively; those of tedizolid were 0.25 and 0.4 mg/L. The MIC50 and MIC90 of tedizolid remained at 0.75 and 1 mg/L against the MLRSA strains (MIC90 ≥ 8 mg/L). Conclusions. Both for MRSA and for MLRSA, the MICs obtained for tedizolid were at least 2 dilutions lower than those of linezolid, thus demonstrating between 2 and 4 times greater activity in vitro than linezolid (AU)

Introducción. La prevalencia de Staphylococcus aureus resistente a la meticilina (SARM) se sitúa en España en torno al 20 y el 30%. Sin embargo, la resistencia a linezolid se reporta de forma excepcional, salvo en algunos brotes nosocomiales. El objetivo de nuestro estudio fue realizar un análisis comparativo de la sensibilidad in vitro de linezolid y tedizolid frente a aislados de SARM, así como frente a otros también resistentes a linezolid (SARLM) mediados por el gen cfr. Material y métodos. Se determinó la sensibilidad in vitro a linezolid y tedizolid mediante la técnica de E-test a 18 cepas SARM y a otras 18 que además presentaban resistencia a linezolid (SARLM) mediadas por el gen cfr, procedentes de aislados clínicos en el Servicio de Microbiología de un Hospital terciario Universitario. Resultados. Todas las cepas de SARM fueron sensibles a ambos antibióticos. Analizando los aislados clínicos de SARM, las CMI50-CMI90 de linezolid fueron 1,5 y 2 mg/L respectivamente y en el caso de tedizolid de 0,25 y 0,4 mg/L. Frente a las cepas de SARLM (CMI90 ≥ 8 mg/L) las CMI50-CMI90 de tedizolid se mantuvieron en 0,75 y 1 mg/L. Conclusiones. Tanto en el caso de las SARM como en el de las SARLM, las CMI obtenidas con tedizolid resultaron ser de al menos dos diluciones más bajas, demostrando entre 2 y 4 veces mayor actividad in vitro que linezolid (AU)

Actualización en Patología Infecciosa 2016 / Update in Infectious Diseases 2016

La resistencia a los antimicrobianos incrementa su impacto sanitario, social y económico. A todos los niveles (estatal, autonómico y local) surgen iniciativas para poder contener el problema de las resistencias. La actualización de este año 2016, estudia aspectos microbiológicos, epidemiológicos y clínicos de las bacterias multirresistentes, así como los recursos para su abordaje terapéutico, desde los fármacos antiguos hasta los modernos, desde las combinaciones terapéuticas hasta la optimización con programas de stewarship. Desde el punto de vista de la infección fúngica se plantean escenarios con nuevas especies de levaduras o nuevos contextos clínicos en hongos filamentosos. En el ámbito pediátrico se analizan homologías y diferencias con la Infección fúngica invasiva del adulto. Por último, en el ámbito de la parasitología, se revisa el tratamiento de la malaria grave importada o el de aquella resistente a antipalúdicos (AU)

Antimicrobial resistance increases it health, social and economic impact. in all areas (state, regional and local), initiatives to try to contain the problem of resistance arise. In the update of this year 2016, we study microbiological, epidemiological and clinical aspects of multi-resistant bacteria, as well as resources for therapeutic approach, from ancient to modern drugs from therapeutic combinations to optimization Stewardship programs. In the case of fungal infection, we analyze clinical scenarios with different species in yeast or new clinical settings in filamentous fungi. Taking paediatric population, homologies and differences with adults in invasive fungal infection were compared. Finally in the field of parasitology, treatment of severe malaria imported or that resistant to antimalarial drugs were reviewed (AU)