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IntroductionCoronavirus disease 2019 (COVID-19) affects the population unequally, with a greater impact on older and immunosuppressed people.MethodsHence, we performed a prospective experimental cohort study to characterise the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in immune-compromised patients (older adults and oncohaematologic patients), compared with healthy counterparts, based on deep characterisation of the circulating immune cell subsets.Results and discussionWhile acquired humoral and cellular memory did not predict subsequent infection 18 months after full vaccination, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, natural killer (NK) cells, monocytes and TEMRA Tγδ cells that were differentially expressed in individuals who were subsequently infected and not infected not just following immunisation, but also prior to vaccination. Of note, we found up to seven clusters within the TEMRA Tγδ cell population, with some of them being expanded and others decreased in subsequently infected individuals. Moreover, some of these cellular clusters were also related to COVID-19-induced hospitalisation in oncohaematologic patients. Therefore, we have identified a cellular signature that even before vaccination is related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV-2 messenger RNA (mRNA) vaccines.

Urinary tract infection (UTI) is a common cause of recurrent infections, especially among young women, but also in patients with infections related to the insertion of urological devices. The aim of this study was to determine the recurrent UTI readmission rate among older patients and the risk factors for recurrent UTI in a prospective cohort of patients admitted to the hospital with community-acquired UTI. We assessed the frequency of recurrent UTIs over a one-year follow-up period after discharge and compared the clinical and epidemiological characteristics between cases with and without recurrences. Out of a total of 462 patients included in this study, 35 (7.6%) had a readmission due to UTI. The patients in the overall series had a median age of 78 (69–86) years, and 50% were women. Recurrent UTIs were associated with healthcare-associated UTIs (OR 2.8, 95% CI 1.1–6.9) and Pseudomonas aeruginosa infections (OR 2.7, 95% CI 1.1–7.2) according to multivariate analysis. Patients with recurrent UTIs experienced longer hospital stays, with no significant difference in mortality rates. Half of the recurrent UTIs were caused by the same microorganisms as those in primary UTIs, but the prolonged period up to recurrence, with a median of 4 months, suggests that they were mostly reinfections. In conclusion, elderly patients admitted to the hospital with complicated UTIs had a low long-term risk of recurrent UTIs. However, this risk was higher in patients with healthcare-associated infection criteria and in those with P. aeruginosa UTIs. Identifying these risk groups may aid in the early detection of recurrent UTIs.

Current influenza vaccines elicit humoral immune responses against the haemagglutinin (HA) protein of influenza viruses. Different antigenic sites have been identified in the HA head as the main target of haemagglutination inhibition (HAI) antibodies (Sb, Sa, Cb, Ca1 and Ca2). To determine immunodominance (ID) of each site, we performed HAI assays against a panel of mutant viruses, each one lacking one of the classically defined antigenic sites and compared it to wild type (Wt). Agglutinating antibodies were measured before and after vaccination in two different regimens: Quadrivalent Influenza Vaccine (QIV) in young adults; or Adjuvanted Trivalent influenza Vaccine (ATIV) in elderly. Our results showed abs before vaccination were significantly reduced against all antigenic sites in the elderly and only against Sb and Ca2 in young adults compared to the Wt. Humoral response to vaccination was significantly reduced against all viruses compared to the Wt for the ATIV and only against Sb and Ca2 for the QIV. The strongest reduction was observed in all cases against Sb followed by Ca2. We concluded that ID profile was clearly dominated by Sb followed by Ca2. Additionally, the antibody response evolved with age, increasing the response towards less immunodominant epitopes of HA head. Adjuvants can positively influence ID hierarchy broadening responses towards multiple antigenic sites of HA head.

Smallpox vaccination may confer cross-protection to mpox. We evaluated vaccinia virus antibodies in 162 persons ≥50 years of age in Spain; 68.5% had detectable antibodies. Highest coverage (78%) was among persons 71–80 years of age. Low antibody levels in 31.5% of this population indicates that addressing their vaccination should be a priority.

ObjectiveAntibodies elicited by seasonal influenza vaccines mainly target the head of hemagglutinin (HA). However, antibodies against the stalk domain are cross-reactive and have been proven to play a role in reducing influenza disease severity. We investigated the induction of HA stalk-specific antibodies after seasonal influenza vaccination, considering the age of the cohorts.MethodsA total of 166 individuals were recruited during the 2018 influenza vaccine campaign (IVC) and divided into groups:

Resumen: Introducción: Las coinfecciones por gripe y otros virus respiratorios (OVR) durante las epidemias gripales son frecuentes. El objetivo de este estudio es examinar las variables demográficas y virológicas relacionadas con las coinfecciones entre la gripe y OVR. Materiales y métodos: En este estudio se analizaron muestras respiratorias de 8 epidemias gripales consecutivas (desde la temporada 2011-2012 hasta la temporada 2018-2019), en las que se había detectado un resultado positivo de gripe mediante test en laboratorio. Analizamos los datos objetivándolos frente a diferentes variables: edad, sexo, tipo de paciente (hospitalizado/centinela) y tipo/subtipo de gripe detectada. Resultados: Las coinfecciones entre gripe y OVR se detectaron en el 17,8% de los casos positivos de gripe. En los niños de entre 0-4 años (OR: 2,7; IC 95%: 2,2-3,4), los niños de entre 5-14 años (OR: 1,6; IC 95%: 1,2-2,1) y los pacientes infectados por el subtipo A(H3N2) (OR: 1,4; IC 95%: 1,14-1,79), se detectó una probabilidad significativamente mayor de detectar estas coinfecciones. Además, observamos que las coinfecciones entre gripe y 2 o más OVR fueron llamativamente más frecuentes en niños de 0-4 años (OR: 0,5; IC 95%: 0,32-0,8), en adultos de entre 40-64 años (OR: 0,5; IC 95%: 0,3-0,9) y en mujeres (OR: 0,7; IC 95%: 0,5-0,9). Discusión: Estos resultados muestran que las coinfecciones entre gripe y OVR son más frecuentes en niños de 0-4 años y de 5-14 años, y en los casos en los que el subtipo A(H3N2) está implicado. Estos datos pueden ser útiles para enfocar el diagnóstico mediante métodos multiplex en aquellos laboratorios que posean pocos recursos económicos y humanos. Abstract: Introduction: Coinfections of influenza and other respiratory viruses (ORVs) are frequent in the epidemic season. The aim of this study was to examine the demographic and virological variables associated with coinfections by influenza and ORVs. Materials and methods: We analysed respiratory samples of patients with laboratory-confirmed influenza using molecular diagnostic methods obtained in 8 consecutive influenza seasons (2011-2012 to 2018-2019). We analysed data focusing on different variables: age, sex, type of patient (hospitalized/sentinel) and detected type/subtype of influenza. Results: Coinfections of influenza and ORVs were detected in 17.8% of influenza-positive samples. The probability of detecting coinfection was significantly higher in young children (0-4 years; OR: 2.7; 95% CI: 2.2-3.4), children (5-14 years; OR: 1.6; 95% CI: 1.2-2.1) and patients infected with the A(H3N2) subtype (OR: 1.4; 95% CI: 1.14-1.79). Also, we found a significantly higher frequency of coinfections involving influenza and 2 or more other respiratory viruses in young children (0-4 years; OR: 0.5; 95% CI: 0.32-0.8), adults (40-64 years; OR: 0.5; 95% CI: 0.3-0.9) and women (OR: 0.7; 95% CI: 0.5-0.9). Discussion: These results show that coinfections of influenza and ORVs are more frequent in young children and children, and in cases involving the A(H3N2) influenza subtype. Our findings can be useful to guide the use of multiplex diagnostic methods in laboratories with limited resources.

Introduction: Coinfections of influenza and other respiratory viruses (ORVs) are frequent in the epidemic season. The aim of this study was to examine the demographic and virological variables associated with coinfections by influenza and ORVs. Materials and methods: We analysed respiratory samples of patients with laboratory-confirmed influenza using molecular diagnostic methods obtained in 8 consecutive influenza seasons (2011–2012 to 2018–2019). We analysed data focusing on different variables: age, sex, type of patient (hospitalized/sentinel) and detected type/subtype of influenza. Results: Coinfections of influenza and ORVs were detected in 17.8% of influenza-positive samples. The probability of detecting coinfection was significantly higher in young children (0–4 years; OR: 2.7; 95% CI: 2.2–3.4), children (5–14 years; OR: 1.6; 95% CI: 1.2–2.1) and patients infected with the A(H3N2) subtype (OR: 1.4; 95% CI: 1.14–1.79). Also, we found a significantly higher frequency of coinfections involving influenza and 2 or more other respiratory viruses in young children (0–4 years; OR: 0.5; 95% CI: 0.32–0.8), adults (40–64 years; OR: 0.5; 95% CI: 0.3–0.9) and women (OR: 0.7; 95% CI: 0.5–0.9). Discussion: These results show that coinfections of influenza and ORVs are more frequent in young children and children, and in cases involving the A(H3N2) influenza subtype. Our findings can be useful to guide the use of multiplex diagnostic methods in laboratories with limited resources. Resumen: Introducción: Las coinfecciones por gripe y otros virus respiratorios (OVR) durante las epidemias gripales son frecuentes. El objetivo de este estudio es examinar las variables demográficas y virológicas relacionadas con las coinfecciones entre la gripe y OVR. Materiales y métodos: En este estudio se analizaron muestras respiratorias de 8 epidemias gripales consecutivas (desde la temporada 2011–2012 hasta la temporada 2018–2019), en las que se había detectado un resultado positivo de gripe mediante test en laboratorio. Analizamos los datos objetivándolos frente a diferentes variables: edad, sexo, tipo de paciente (hospitalizado/centinela) y tipo/subtipo de gripe detectada. Resultados: Las coinfecciones entre gripe y OVR se detectaron en el 17,8% de los casos positivos de gripe. En los niños de entre 0-4 años (OR: 2,7; IC 95%: 2,2–3,4), los niños de entre 5-14 años (OR: 1,6; IC 95%: 1,2–2,1) y los pacientes infectados por el subtipo A(H3N2) (OR: 1,4; IC 95%: 1,14–1,79), se detectó una probabilidad significativamente mayor de detectar estas coinfecciones. Además, observamos que las coinfecciones entre gripe y 2 o más OVR fueron llamativamente más frecuentes en niños de 0–4 años (OR: 0,5; IC 95%: 0,32–0,8), en adultos de entre 40–64 años (OR: 0,5; IC 95%: 0,3–0,9) y en mujeres (OR: 0,7; IC 95%: 0,5–0,9). Discusión: Estos resultados muestran que las coinfecciones entre gripe y OVR son más frecuentes en niños de 0–4 años y de 5–14 años, y en los casos en los que el subtipo A(H3N2) está implicado. Estos datos pueden ser útiles para enfocar el diagnóstico mediante métodos multiplex en aquellos laboratorios que posean pocos recursos económicos y humanos.

Abstract Infection (either community acquired or nosocomial) is a major cause of morbidity and mortality in critical care medicine. Sepsis is present in up to 30% of all ICU patients. A large fraction of sepsis cases is driven by severe community acquired pneumonia (sCAP), which incidence has dramatically increased during COVID-19 pandemics. A frequent complication of ICU patients is ventilator associated pneumonia (VAP), which affects 10–25% of all ventilated patients, and bloodstream infections (BSIs), affecting about 10% of patients. Management of these severe infections poses several challenges, including early diagnosis, severity stratification, prognosis assessment or treatment guidance. Digital PCR (dPCR) is a next-generation PCR method that offers a number of technical advantages to face these challenges: it is less affected than real time PCR by the presence of PCR inhibitors leading to higher sensitivity. In addition, dPCR offers high reproducibility, and provides absolute quantification without the need for a standard curve. In this article we reviewed the existing evidence on the applications of dPCR to the management of infection in critical care medicine. We included thirty-two articles involving critically ill patients. Twenty-three articles focused on the amplification of microbial genes: (1) four articles approached bacterial identification in blood or plasma; (2) one article used dPCR for fungal identification in blood; (3) another article focused on bacterial and fungal identification in other clinical samples; (4) three articles used dPCR for viral identification; (5) twelve articles quantified microbial burden by dPCR to assess severity, prognosis and treatment guidance; (6) two articles used dPCR to determine microbial ecology in ICU patients. The remaining nine articles used dPCR to profile host responses to infection, two of them for severity stratification in sepsis, four focused to improve diagnosis of this disease, one for detecting sCAP, one for detecting VAP, and finally one aimed to predict progression of COVID-19. This review evidences the potential of dPCR as a useful tool that could contribute to improve the detection and clinical management of infection in critical care medicine.

IntroductionExternal Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods.MethodsWe invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays.ResultsWithin run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization.DiscussionThis study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.

IntroductionThe third dose of the COVID-19 vaccine is especially necessary in people over 65 years of age due to their lower immune response.MethodsWe designed a multicentre, prospective observational study including 98 people ≤65 years old who lived in two nursing homes in Valladolid, Spain. One of the groups had previous experience with SARS-CoV-2 (n=68;69.4%) and the other was naïve (n=30;30.6%). We evaluated the response to the three doses of the Comirnaty vaccine and the dynamics of antibodies during 5 consecutive serum samplings: 2 after the first two doses of vaccination, one three months after the first dose, another at 6 months and the last one month after the third dose. IgG antibodies against SARS-CoV-2 S1, RBD and N antigens were analysed.ResultsBoth groups increased the level of Abs against S1 and RBD, but the experienced group showed a 130-fold higher humoral response due to hybrid immunisation (infection+vaccination). The response to vaccination with Comirnaty against COVID-19 was higher in those ≤65 years with previous experience than those who were naïve. However, the amount of antibodies against S1 and RBD equalised at 6 months. After the third dose, both groups raised the amount of antibodies to a similar level. The reinfections suggested by the analysis of antibodies against N were frequent in both groups.DiscussionThe third dose showed a clear benefit for elderly people, with the reinforcement of the antibody levels after the decline suffered after six months of the first two doses.

Abstract Introduction Previous studies have described some risk factors for multidrug-resistant (MDR) bacteria in urinary tract infection (UTI). However, the clinical impact of MDR bacteria on older hospitalized patients with community-acquired UTI has not been broadly analyzed. We conducted a study in older adults with community-acquired UTI in order to identify risk factors for MDR bacteria and to know their clinical impact. Methods Cohort prospective observational study of patients of 65 years or older, consecutively admitted to a university hospital, diagnosed with community-acquired UTI. We compared epidemiological and clinical variables and outcomes, from UTI due to MDR and non-MDR bacteria. Independent risk factors for MDR bacteria were analyzed using logistic regression. Results 348 patients were included, 41.4% of them with UTI due to MDR bacteria. Median age was 81 years. Hospital mortality was 8.6%, with no difference between the MDR and non-MDR bacteria groups. Median length of stay was 5 [4–8] days, with a longer stay in the MDR group (6 [4–8] vs. 5 [4–7] days, p = 0.029). Inadequate empirical antimicrobial therapy (IEAT) was 23.3%, with statistically significant differences between groups (33.3% vs. 16.2%, p

Aim: This study aimed to evaluate clinically significant sex differences that could have an effect on the choice of treatment and outcomes of urinary tract infection (UTI) in aged 80 and over hospitalized patients with community-acquired UTI. Methods: This was a prospective study of 161 patients aged 80 and over admitted to hospital with community-acquired UTI. Epidemiological, clinical, laboratory and microbiologic variables were compared between both sexes. Multivariate analysis was performed using logistic regression to determine the variables independently associated with sex. Results: In a population of 91 (56.52%) women and 70 (43.48%) men, aged 80 and over, we found that women were more likely to have cognitive impairment (p = 0.035) and less likely to have chronic obstructive pulmonary disease (COPD) (p = 0.006) and indwelling urinary catheter (p < 0.001) than men. Levels of creatinine were higher in men than in women (p = 0.008). Septic shock at presentation was more frequent in the male group (p = 0.043). Men had a higher rate of polymicrobial infection (p = 0.035) and Pseudomonas aeruginosa infection (p = 0.003). Factors independently associated with sex by multivariate analysis were septic shock, cognitive impairment, COPD and indwelling urinary catheter. Conclusion: Men aged 80 and over with community-acquired UTI had more septic shock at admission to hospital and higher rates of indwelling urinary catheter, while women had more cognitive impairment. There were no differences in outcomes between sexes.

Bacteremia has been associated with severity in some infections; however, its impact on the prognosis of urinary tract infections (UTIs) is still disputed. Our goal is to determine the risk factors for bacteremia and its clinical impact on hospitalized patients with complicated community-acquired urinary tract infections. We conducted a prospective observational study of patients admitted to the hospital with complicated community-acquired UTIs. Clinical variables and outcomes of patients with and without bacteremia were compared, and multivariate analysis was performed to identify risk factors for bacteremia and mortality. Of 279 patients with complicated community-acquired UTIs, 37.6% had positive blood cultures. Risk factors for bacteremia by multivariate analysis were temperature ≥ 38 °C (p = 0.006, OR 1.3 (95% CI 1.1–1.7)) and procalcitonin ≥ 0.5 ng/mL (p = 0.005, OR 8.5 (95% CI 2.2–39.4)). In-hospital and 30-day mortality were 9% and 13.6%, respectively. Quick SOFA (p = 0.030, OR 5.4 (95% CI 1.2–24.9)) and Barthel Index p = 0.020, OR 4.8 (95% CI 1.3–18.2)) were associated with 30-day mortality by multivariate analysis. However, bacteremia was not associated with 30-day mortality (p = 0.154, OR 2.7 (95% CI 0.7–10.3)). Our study found that febrile community-acquired UTIs and elevated procalcitonin were risk factors for bacteremia. The outcomes in patients with bacteremia were slightly worse, but without significant differences in mortality.

Urinary tract infection (UTI) is a common condition that predominantly affects elderly people, who are particularly susceptible to developing sepsis. Previous studies have indicated a detrimental effect of sepsis on short-term outcomes in elderly patients with UTI, but there is a lack of data about the middle-term prognosis. The aim of this study was to investigate the influence of sepsis on the middle-term prognosis of patients aged 65 years or older with complicated community-acquired UTIs. A prospective observational study of patients admitted to a hospital with UTI. We conducted a comparison of epidemiological and clinical variables between septic and nonseptic patients with UTI, as well as their 6-month case-fatality rate. A total of 412 cases were included, 47.8% of them with sepsis. Septic patients were older (83 vs. 80 years, p < 0.001), but did not have more comorbidities. The short-term case-fatality rate was higher in septic patients and this difference persisted at 6 months (34% vs. 18.6%, p = 0.003). Furthermore, age older than 75 years, Barthel index

Risk factors for multidrug-resistant bacteria (MDRB) in nosocomial urinary tract infection (UTI) have been widely studied. However, these risk factors have not been analyzed in community-acquired urinary sepsis (US), nor have its outcomes been studied. The aim of our study is to determine risk factors for MDRB in community-acquired US and its influence on outcomes. Prospective observational study of patients with community-acquired US admitted to a university hospital. We compared epidemiological and clinical variables and outcomes of US due to MDRB and non-MDRB. Independent risk factors for MDRB were analyzed using logistic regression. A total of 193 patients were included, 33.7% of them with US due to MDRB. The median age of patients was 82 years. Hospital mortality was 17.6%, with no difference between the MDRB and non-MDRB groups. The length of hospital stay was 5 (4–8) days, with a non-significant tendency to longer hospital stays in the MDRB group (6 (4–10) vs. 5 (4–8) days, p = 0.051). Healthcare-associated US was found to be an independent risk factor for MDR bacteria by multivariate analysis. In conclusion, the impact of MDR bacteria on the outcomes of community-acquired urinary sepsis was mild. Healthcare-associated US was an independent risk factor for MDR bacteria.

Abstract Background COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p

Fluoroquinolones (FQs) have been widely used for treating urinary tract infections (UTIs); however, the increasing emergence of resistant strains has compromised their use. We aimed to know the usefulness of FQs for the treatment of community-acquired UTI in a setting with a high prevalence of fluoroquinolone-resistant microorganisms. A prospective observational study of patients diagnosed with community-acquired UTI was conducted, in which their outcomes according to whether they had FQs or not in their empirical and directed treatments were compared. A multivariate analysis was performed to identify risk factors for UTIs due to ciprofloxacin-resistant microorganisms. A total of 419 patients were included; 162 (38.7%) patients were treated with FQs, as empirical treatment in 27 (6.4%), and as directed treatment in 135 (32.2%). In-hospital mortality (2.2% vs. 6.6%, p 0.044) and 30-day mortality (4.4 vs. 11%, p 0.028) were both lower in the group of patients directly treated with FQ, while there were no differences when FQs were used as empirical treatment. A total of 37.2% of the cases were resistant to ciprofloxacin, which was associated with healthcare-associated UTI (OR 2.7, 95% CI 2–3.7) and prior exposure to FQs (OR 2.7, 95 % CI 1.9–3.7). In conclusion, our findings show that in a setting with a high prevalence of community-acquired UTI caused by quinolone-resistant microorganisms, FQs as directed treatment for community-acquired UTI were associated with better outcomes than other antibiotics, but their use as empirical treatment is not indicated, even in those cases without risk factors for quinolones resistance.

Influenza B is accountable for an important burden during flu epidemics, causing special impact in children and the elderly. Vaccination is the best approach to address influenza infections. However, one of the main problems of this virus is that two different lineages circulate together, Victoria and Yamagata; and trivalent vaccines, that only contain one of these lineages, are still in use. For that reason, if during an epidemic, the lineage not included in the vaccine predominates, a mismatch would occur, and the vaccine effectiveness will be very poor. In this work, we evaluated the cross-protection given by the trivalent Influenza vaccine and compared serological profiles based on age, sex, and the type of vaccine used. We performed a retrospective analysis of serum samples obtained before and after seasonal influenza vaccination during 20 seasons (1998–2018). The results showed that heterotypic reactivity between both influenza B lineages is common, but always lower than the homologous response. Age is a relevant factor for this cross-reactivity between both lineages, while the sex and the type of vaccine not. Vaccination with trivalent influenza vaccines elicits cross-reactive antibodies against both lineages, however, this response might not be enough to provide an appropriate serological protection in case of mismatch.

BackgroundSex differences in immune responses are well known. However, the humoral response in males and females in the case of influenza vaccination is yet to be characterized since studies have shown uneven results.MethodsA retrospective study was conducted in 2,243 individuals (46.9% males) divided by age (15–64 and ≥65 years old). A serological analysis was performed by hemagglutination inhibition assay (HI) just before and 28 days after annual vaccination against seasonal influenza viruses in people vaccinated during the 2006–2018 seasons. A comparison of the humoral responses against influenza A and B viruses contained in the vaccine, between male and female individuals in young adults and elderly was conducted.ResultsSignificative higher humoral response against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B/Victoria lineage in terms of seroconversion rate were found in elderly women. No significant differences were found in the case of A(H3N2) subtype.ConclusionsElderly women seem to display a greater humoral response against classical A(H1N1), pandemic A(H1N1)pmd09 and B/Victoria lineage than elderly men. Sex dimorphism does not affect young adults.

Influenza viruses provide a great threat for the human population, causing highly contagious respiratory infections that can lead to serious clinical complications. There are a limited variety of influenza antivirals, and these antivirals are subjected to the constant emergence of resistances. Therefore, the development of new antiviral strategies to combat influenza viruses and other RNA viruses must be promoted. In this work, we design a proof-of-concept of a recently described CRISPR/Cas tool that has been proposed as a possible future RNA virus antiviral, named CRISPR/CasRx. For this, we verified the efficiency of the CasRx endonuclease in the degradation of the eGFP mRNA reporter gene and we established the best conditions for, and the efficient performance of, the CRISPR/CasRx system. The results were measured by fluorescence microscopy, flow cytometry, and qRT-PCR. The analyses demonstrated a reduction in fluorescence, regardless of the amount of eGFP reporter plasmid transfected. The analyses showed an 86–90% reduction in fluorescence by flow cytometry and a 51–80% reduction in mRNA expression by qRT-PCR. Our results demonstrate that the CasRx endonuclease is an efficient tool for eGFP mRNA knockdown. Therefore, subsequent experiments could be useful for the development of a new antiviral tool.

The use of non-pharmaceutical interventions (NPIs), such as social distancing, lockdowns and the massive use of masks, have not only largely prevented the spread of SARS-CoV-2, but also of other respiratory viruses such as influenza or respiratory syncytial virus (RSV). This decrease has been so high that, in most countries, the influenza and RSV epidemic has not occurred. Far from being a beneficial fact, this can be problematic, since the absence of circulation of certain pathogens can lead to a decrease in herd immunity against them. This can promote the rise of more serious, longer-lasting epidemics that start sooner. To alleviate the collateral effects that may occur due to the decrease in circulation of viruses such as influenza, it is necessary to increase the production of influenza vaccines, carry out mass vaccination campaigns and focus on vaccinating the main drivers of this virus, children.

An extensively drug-resistant (XDR) Klebsiella pneumoniae isolate MS3802 from a tracheostomy exudate was whole-genome sequenced using MiSeq and Oxford Nanopore MinION platforms in order to identify the antimicrobial resistance and virulence determinates and their genomic context. Isolate MS3802 belonged to the clone ST23 and presented a capsular serotype K1, associated with hypervirulent K. pneumoniae (hvKp) isolates. The isolate harboured a chromosomally encoded blaCTX-M-15 gene and contained a large IncHI1B hybrid virulence/resistance plasmid carrying another copy of the blaCTX-M-15 and the virulence factors iucABCD-iutA, iroBCDN, rmpA and rmpA2. The carbapenemase gene blaOXA-48 was found in a Tn1999-like transposon and the 16S rRNA methylase armA gen located in the vicinity of other antibiotic-resistant genes on an IncM2 plasmid. This study represents, to the best of our knowledge, the first description of a blaCTX-M-15-, blaOXA-48- and armA-harbouring K. pneumoniae of ST23 and capsular serotype K1 in Spain. Our report emphasizes the importance of implementing new surveillance strategies to monitor the risk of emergence and spread of such XDR and hypervirulent K. pneumoniae isolates.

La formación de especialistas en ciencias de la salud se ha mantenido casi inalterada durante varias décadas, pero a partir de la publicación del Real Decreto de Troncalidad, de reespecialización troncal y áreas de capacitación específica, el clásico sistema MIR puede sufrir profundos cambios. Repasamos en este artículo la evolución del mismo en nuestro país.

Background: vaccination is the best approach to prevent influenza infections so far. Serological studies on the effect of different vaccine types are important to address vaccination campaigns and protect our population. In our study, we compared the serological response against influenza A subtypes using the non-adjuvanted influenza vaccine (NAIV) in adults and the elderly and the adjuvanted influenza vaccine (AIV) in the elderly. Methods: We performed a retrospective analysis by hemagglutination inhibition assay (HI) of serum samples right before and 28 days after seasonal influenza vaccination during the 1996–2017 seasons. Conclusions: The AIV presents better performance against the A(H3N2) subtype in the elderly whereas the NAIV induces a better response against A(H1N1)pdm09 in the same group.

Little information on the SARS-CoV-2 virus in animals is available to date. Whereas no one husbandry animal case has been reported to date, which would have significant implications in food safety, companion animals play a role in COVID-19 epidemiology that opens up new questions. There is evidence that SARS-CoV-2 can infect felines, dogs and minks, and there is evidence of human-to-animal infection. Likewise, the S protein nucleotide sequence of the SARS-CoV-2 virus isolated in domestic animals and humans is identical, and the replication of the SARS-CoV-2 in cats is efficient. Besides, the epidemiological evidence for this current pandemic indicates that the spillover to humans was associated with close contact between man and exotic animals, very probably in Chinese wet markets, thus there is a growing general consensus that the exotic animal markets, should be strictly regulated. The examination of these findings and the particular role of animals in COVID-19 should be carefully analyzed in order to establish preparation and containment measures. Animal management and epidemiological surveillance must be also considered for COVID-19 control, and it can open up new questions regarding COVID-19 epidemiology and the role that animals play in it.

The objective of this study was to evaluate the capacity of 49 methicillin resistant Staphylococcus aureus (MRSA) from foods of animal origin (42 from dairy products and 7 from meat and meat products) to form biofilms. Overall, a higher biofilm biomass was observed for those MRSA strains harboring SCCmec type IV, while 8 MRSA strains (5 from dairy products and 3 from meat and meat products) were classified as strong biofilm formers in standard Tryptic Soy Broth medium. When a prolonged incubation period (48 h) was applied for those 8 MRSA strains, an increased biofilm biomass accumulation was observed during the time course, whereas the number of viable cells within the biofilms decreased as the biomass increased. The capacity of biofilm production correlated pretty well between the experiments using polystyrene microtiter plates and stainless steel micro-well plates, and significant higher values were observed in stainless steel when glucose was added to TSB during the enrichment. Biofilms were further characterized by confocal laser scanning microscope (CLSM), confirming that proteins and α-polysaccharides were the predominant components inside the extracellular polymeric matrix of biofilms formed by MRSA strains. In conclusion, our results confirm that MRSA isolates from foods of animal origin have significant capacity for forming biofilms with a high protein content, which can play a key role for the successful dissemination of MRSA lineages via food. Knowledge of the capacity of MRSA strains to produce biofilms, as well as characterization of the main MRSA biofilms matrix components, can help both to counteract the mechanisms involved in biofilm formation and resistance and to define more rational control strategies by using tailor-made cleaning agents.

Introducción: Este estudio pretende determinar las semanas de alta circulación de rotavirus en valladolid, y comparar las características de los ingresos y urgencias en período epidémico con respecto al período no epidémico. Métodos: Se utilizaron las declaraciones al sistema de información microbiológica, el conjunto mínimo básico de datos y el registro de urgencias. Se calcularon los casos esperados para 2006 a partir de un modelo elaborado previamente. Si los casos observados superaban el umbral superior del 95% de los esperados, la semana se consideró epidémica. Se compararon las características de los ingresos y urgencias en ambos períodos. Resultados: En 2006 se diagnosticaron un 42% menos de los casos esperados. La media de ingresos diarios fue superior en período epidémico (diferencia=1,49; p=0,01), y también fue mayor la duración media del ingreso. Conclusión: La actividad del servicio de pediatría se incrementó en período epidémico, por lo que es oportuna la implantación de actividades de vigilancia, programas de prevención y control frente a rotavirus en el ámbito hospitalario.Introduction: The aim of this study was to determine the weeks of high rotavirus circulation in Valladolid (Spain) and to compare the characteristics of hospitalizations and emergencies in epidemic and nonepidemic periods. Methods: The information sources consisted of the weekly notifications to the Microbiological Information System, the Minimum Data Set, and the Emergency Registry. Expected cases for 2006 were calculated using a previously developed model. Weeks with observed cases over the upper limit of the 95% confidence interval for expected cases were considered epidemic periods. Hospitalization and emergencies in epidemic and nonepidemic periods were compared. Results: The number of cases in 2006 was 42% less than the expected number. The mean number of daily admissions was higher in epidemic periods (d=1.49; p=0.01) and the length of admissions was longer. Conclusion: The activity of the paediatric service increased during the epidemic period. Consequently, implementation of surveillance activities and prevention and control programs for rotavirus in hospitals would seem advisable.

Fundamento: El Campylobacter es uno de los principales patógenos entéricos, sin embargo algunos aspectos de su epidemiología no se conocen con precisión. El objetivo de este trabajo es analizar en la provincia de Valladolid la tendencia y variación estacional de las gastroenteritis que provoca. Métodos: Se realizó un análisis de series temporales mediante un modelo aditivo a partir de las declaraciones realizadas al Sistema de Información Microbiológico por los dos principales hospitales de la provincia de Valladolid. Se consideró como caso a los pacientes que presentaron un coprocultivo con un aislamiento de Campylobacter spp. en el período 2000- 2004. Se determinaron la tendencia, los coeficientes estacionales de la serie de casos, las tasas de incidencia en función de la edad, el sexo y el año de declaración y las razones de tasas. Resultados: Se observó una tendencia descendente en la declaración de casos durante el periodo de estudio y se detectó un coeficiente estacional significativo en la cuatrisemana seis (c=12,854, p=0,023). La tasa de incidencia fue mayor en los menores de cinco años y en los hombres, ascendiendo a 1841,9 casos (IC 95: 1797,2-1889,6) y 99,7 casos (IC 95% 96,9-102,4) por 100.000 habitantes-año respectivamente. Conclusiones: La infección por Campylobacter tiene lugar en mayor medida en la época del final de la primavera, afectando principalmente a los niños. Es necesario profundizar en el conocimiento de la epidemiología de este microorganismo a nivel local con un abordaje multidisciplinar que considere tanto aspectos microbiológicos como epidemiológicos.

Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad response of heterotypic antibodies against avian influenza viruses, albeit at a low level.

Fun da men to: El ele vado con su mo de an ti bió ti cos sis té mi - cos en nues tro país hace ne cesario el es tu dio de aque llos fac to - res que de ter mi nen su dis tri bu ción. Di versos pa rá me tros es tán im pli ca dos en el re par to de si gual de su con sumo, en tre ellos: a) la epi de mio lo gía de los pro ce sos in fec cio sos, b) los fac tores de - pen dien tes de la po bla ción y c) fac to res de pen dien tes de los mé di cos pres crip to res. En el pre sen te tra ba jo pre ten de mos rea - li zar un aná li sis de aque llos de ter mi nan tes de pen dien tes de la po bla ción (tipo de po bla ción y edad). Mé to dos: Estu dio lon gitudinal re tros pec ti vo con da tos de con su mo de an ti bió ti cos de uso sis té mi co pro por cio na dos por la com pa ñía Inter na tio nal Mar ke ting Ser vices (IMS) en tre el 1 de ene ro de 1996 y el 31 de di ciem bre del 2000. El in di ca dor de con su mo uti li za do fue el nú me ro de do sis dia ria de fi ni da por 1000 ha bi tan tes y día (DHD). Se con si de ra ron seis áreas geo - grá fi cas en la pro vin cia de Va lla do lid, tres de ellas de ca rác ter ur ba no y otras tres pre do mi nan te men te ru ra les. Re sul ta dos: El con su mo glo bal por área fue el si guien te: Me di na del Cam po (25,9DHD), Va lla do lid ca pi tal (23,4DHD), La gu na de Due ro (22,6DHD), Área Nor te (22,4DHD), Área Sur (21,4DHD) y en úl ti mo lu gar el Área Cen tro (20,2DHD). El con su mo es pe cí fi co por áreas de ter mi nó un ma yor con su mo de amo xi ci li na en las tres áreas ur ba nas, amo xi ci li na-cla vu lá ni - co y los prin ci pa les ma cró li dos en Me di na del Cam po, qui no lo - nas en el Área Nor te y te traciclinas y sul fa mi das en Va lladolid ca pi tal Con clu sio nes: Obser va mos di fe ren cias glo ba les de con su - mo im portantes en tre áreas, con unos má xi mos en las áreas ur - ba nas. Estas di fe ren cias fue ron más mar ca das al es tu diar la dis - tri bu ción geo grá fi ca del con su mo de los prin ci pa les prin cipios ac ti vos.

Anorexia nervosa (AN) is the most prevalent of eating disorders in children and adolescents, and its treatment is long and complex, involving a multidisciplinary team. Nutritional rehabilitation and restoration of a healthy body weight is one of the central goals in the initial stages of inpatient treatment. However, current recommendations on initial energy requirements for these patients are inconsistent, with a clear lack of controlled studies, available scientific evidence and global consensus on the most effective and safe refeeding practices in hospitalized adolescents with anorexia nervosa (AN). Conservative refeeding recommendations have been classically established in order to prevent the refeeding syndrome. Nevertheless, various works have recently appeared advocating a higher initial caloric intake, without observing more complications or refeeding syndrome, and allowing a shorter average stay. We present our experience in the treatment of restricting AN with a conservative progressive treatment. We have obtained good results with this approach, which was well tolerated by patients, with no observing complications. As a consequence, the medical team could establish a pact about the therapeutic goals with the patients in an easier way.