Search

In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge. Aims This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children. Methods We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome-related knowledge for translation to clinical practice. Results and conclusion The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so-called microbiome thinking into our routine clinical practice.

Introduction: In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods: A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results: A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P = .014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed. Conclusions: In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved. Resumen: Introducción: En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento. Material y métodos: Estudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de 16 años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con >40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012. Resultados: Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (P = ,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso. Conclusiones: En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria.

Resumen: Introducción: En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento. Material y métodos: Estudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de 16 años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con > 40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012. Resultados: Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (p = 0,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso. Conclusiones: En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria. Abstract: Introduction: In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods: A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients > 16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with > 40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results: A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P = .014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed. Conclusions: In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved.

Purpose We aimed to compare complication rates and functional outcomes in patients with bilateral mandibular fractures treated with different degrees of internal fixation rigidity. Patients and Methods This international, multicenter randomized controlled trial included adults with bilateral mandibular fractures located at either the angle and body, angle and symphysis, or body and symphysis. Patients were treated with either a combination of rigid fixation for the anterior fracture and nonrigid fixation for the posterior fracture (mixed fixation) or nonrigid fixation for both fractures. The primary outcome was complications within 6 weeks after surgery. Secondary outcomes were complications within 3 months, Helkimo dysfunction index, and mandibular mobility at 6 weeks and 3 months after surgery. Results Of the 315 patients enrolled, 158 were randomized to the mixed fixation group and 157 to the nonrigid fixation group. The overall complication rate at 6 weeks in the intention-to-treat population was 9.6% (95% confidence interval [CI], 5.3% to 15.6%) in the mixed fixation group and 7.8% (95% CI, 4.0% to 13.5%) in the nonrigid fixation group. With an unadjusted odds ratio of 1.25 (95% CI, 0.51 to 3.17), there were no statistically significant differences in complication rates between the 2 groups (P = .591). A multivariable model for complication risk at 6 weeks found no significant differences between treatment groups, but patients with moderate or severe displacement had a higher complication rate than those with no or minimal displacement (adjusted odds ratio, 4.58; 95% CI, 1.16 to 18.06; P = .030). There were no significant between-group differences in complication rates at 3 months. Moreover, no significant differences in Helkimo dysfunction index and mandibular mobility index at 6 weeks and 3 months were found between groups according to treatment allocated and treatment received. Conclusions A combination of rigid and nonrigid fixation in patients with bilateral mandibular fracture has similar complication rates and functional outcomes to nonrigid fixation for both fractures.

TIPICO is an expert meeting and workshop that aims to provide the most recent evidence in the field of infectious diseases and vaccination. The 10th Interactive Infectious Disease TIPICO workshop took place in Santiago de Compostela, Spain, on November 21–22, 2019. Cutting-edge advances in vaccination against respiratory syncytial virus, Streptococcus pneumoniae, rotavirus, human papillomavirus, Neisseria meningitidis, influenza virus, and Salmonella Typhi were discussed. Furthermore, heterologous vaccine effects were updated, including the use of Bacillus Calmette-Guérin (BCG) vaccine as potential treatment for type 1 diabetes. Finally, the workshop also included presentations and discussion on emergent virus and zoonoses, vaccine resilience, building and sustaining confidence in vaccination, approaches to vaccine decision-making, pros and cons of compulsory vaccination, the latest advances in decoding infectious diseases by RNA gene signatures, and the application of big data approaches.

Emerging studies from SARS-CoV-2-infected patients indicate a preponderant role of monocytes/macrophages in the pathogenesis of this viral infection, in a similar way to that previously observed in other coronavirus outbreaks (SARS and MERS). The clinical presentation of severe patients resembles viral-associated hemophagocytic syndrome, a rare condition previously seen during lethal influenza pandemics and during previous SARS and MERS coronavirus outbreaks. SARS-CoV-2 infection triggers an over-exuberant inflammatory response due to the development of a cytokine storm and the depletion of the adaptative immune compartment, which may prelude sepsis in many cases. The present review summarizes past evidence on the role of monocytes/macrophages in previous coronavirus outbreaks and the emerging knowledge on their role in COVID-19 pathogenesis. Treatment strategies incorporating the blockade of migration and differentiation of monocyte-macrophage, such as granulocyte macrophage-colony stimulating factor inhibitors, might enhance the promising results seen so far with selective cytokine blockade.

ObjectiveMost studies on febrile children have focused on infants and young children with serious bacterial infection (SBI). Although population studies have described an increased risk of sepsis in adolescents, little is known about febrile adolescents attending the emergency department (ED). We aimed to describe patient characteristics and management of febrile adolescents attending the ED.Design and settingThe MOFICHE/PERFORM study (Management and Outcome of Febrile Children in Europe/Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union), a prospective multicentre study, took place at 12 European EDs. Descriptive and multivariable regression analyses were performed, comparing febrile adolescents (12–18 years) with younger children in terms of patient characteristics, markers of disease severity (vital signs, clinical alarming signs), management (diagnostic tests, therapy, admission) and diagnosis (focus, viral/bacterial infection).Results37 420 encounters were included, of which 2577 (6.9%) were adolescents. Adolescents were more often triaged as highly urgent (38.9% vs 34.5%) and described as ill appearing (23.1% vs 15.6%) than younger children. Increased work of breathing and a non-blanching rash were present less often in adolescents, while neurological signs were present more often (1% vs 0%). C reactive protein tests were performed more frequently in adolescents and were more often abnormal (adjusted OR (aOR) 1.7, 95% CI 1.5 to 1.9). Adolescents were more often diagnosed with SBI (OR 1.8, 95% CI 1.6 to 2.0) and sepsis/meningitis (OR 2.3, 95% CI 1.1 to 5.0) and were more frequently admitted (aOR 1.3, 95% CI 1.2 to 1.4) and treated with intravenous antibiotics (aOR 1.7, 95% CI 1.5 to 2.0).ConclusionsAlthough younger children presented to the ED more frequently, adolescents were more often diagnosed with SBI and sepsis/meningitis. Our data emphasise the importance of awareness of severe infections in adolescents.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants and young children worldwide. Here we evaluated host demographic and viral factors associated with RSV disease severity in 325 RSV-infected infants under 1 year of age from 3 European countries during 2017–2020. Younger infants had a higher clinical severity (ReSViNET) score and were more likely to require hospitalization, intensive care, respiratory support, and/or mechanical ventilation than older infants ( Clinical Trials Registration NCT03756766.

Objective Most studies on febrile children have focused on infants and young children with serious bacterial infection (SBI). Although population studies have described an increased risk of sepsis in adolescents, little is known about febrile adolescents attending the emergency department (ED). We aimed to describe patient characteristics and management of febrile adolescents attending the ED. Design and setting The MOFICHE/PERFORM study (Management and Outcome of Febrile Children in Europe/Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union), a prospective multicentre study, took place at 12 European EDs. Descriptive and multivariable regression analyses were performed, comparing febrile adolescents (12-18 years) with younger children in terms of patient characteristics, markers of disease severity (vital signs, clinical alarming signs), management (diagnostic tests, therapy, admission) and diagnosis (focus, viral/bacterial infection). Results 37 420 encounters were included, of which 2577 (6.9%) were adolescents. Adolescents were more often triaged as highly urgent (38.9% vs 34.5%) and described as ill appearing (23.1% vs 15.6%) than younger children. Increased work of breathing and a non-blanching rash were present less often in adolescents, while neurological signs were present more often (1% vs 0%). C reactive protein tests were performed more frequently in adolescents and were more often abnormal (adjusted OR (aOR) 1.7, 95% CI 1.5 to 1.9). Adolescents were more often diagnosed with SBI (OR 1.8, 95% CI 1.6 to 2.0) and sepsis/meningitis (OR 2.3, 95% CI 1.1 to 5.0) and were more frequently admitted (aOR 1.3, 95% CI 1.2 to 1.4) and treated with intravenous antibiotics (aOR 1.7, 95% CI 1.5 to 2.0). Conclusions Although younger children presented to the ED more frequently, adolescents were more often diagnosed with SBI and sepsis/meningitis. Our data emphasise the importance of awareness of severe infections in adolescents. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

EU multicentre ED study of presenting vital signs in >5000 febrile children with an association between “shock index” and serious illness, but low sensitivity limits utility in screening. Objective (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children. Design/setting Observational study in 11 European EDs (2017-2018). Patients Febrile children with measured blood pressure. Main outcome measures Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs). Results Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8. Conclusions High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED.

BackgroundPediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment.MethodsIn this prospective multicenter cohort study, children with POAIs were selected from the European Union Childhood Life-threatening Infectious Diseases Study (EUCLIDS) database to analyze their demographic, clinical, and microbiological data.ResultsA cohort of 380 patients with POAIs, 203 with osteomyelitis (OM), 158 with septic arthritis (SA), and 19 with both OM and SA, was analyzed. Thirty-five patients were admitted to the Pediatric Intensive Care Unit; out of these, six suffered from shock, one needed an amputation of the right foot and of four left toes, and two had skin transplantation. According to the Pediatric Overall Performance Score, 36 (10.5%) showed a mild overall disability, 3 (0.8%) a moderate, and 1 (0.2%) a severe overall disability at discharge. A causative organism was detected in 65% (247/380) of patients.Staphylococcus aureus(S. aureus) was identified in 57.1% (141/247) of microbiological confirmed cases, including 1 (0.7%) methicillin-resistantS. aureus(MRSA) and 6 (4.2%) Panton-Valentine leukocidin (PVL)-producingS. aureus, followed by Group AStreptococcus(18.2%) andKingella kingae(8.9%).K. kingaeand PVL production inS. aureuswere less frequently reported than expected from the literature.ConclusionPOAIs are associated with a substantial morbidity in European children, withS. aureusbeing the major detected pathogen. In one-third of patients, no causative organism is identified. Our observations show an urgent need for the development of a vaccine againstS. aureusand for the development of new microbiologic diagnostic guidelines for POAIs in European pediatric hospitals.

Objective (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children. Design/setting Observational study in 11 European EDs (2017–2018). Patients Febrile children with measured blood pressure. Main outcome measures Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs). Results Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8. Conclusions High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED., EU multicentre ED study of presenting vital signs in >5000 febrile children with an association between "shock index" and serious illness, but low sensitivity limits utility in screening.

Three-dimensional printing (3DP) has recently gained importance in the medical industry, especially in surgical specialties. It uses different techniques and materials based on patients’ needs, which allows bioprofessionals to design and develop unique pieces using medical imaging provided by computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, the Department of Biology and Medicine and the Department of Physics and Engineering, at the Bioastronautics and Space Mechatronics Research Group, have managed and supervised an international cooperation study, in order to present a general review of the innovative surgical applications, focused on anatomical systems, such as the nervous and craniofacial system, cardiovascular system, digestive system, genitourinary system, and musculoskeletal system. Finally, the integration with augmented, mixed, virtual reality is analyzed to show the advantages of personalized treatments, taking into account the improvements for preoperative, intraoperative planning, and medical training. Also, this article explores the creation of devices and tools for space surgery to get better outcomes under changing gravity conditions.

BackgroundCOVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences.Methods and findingsWe carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. We then used a differential expression approach and pathways analysis to detect tissue specific immune severity signals in COVID-19 patients.Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were shown in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis.ConclusionsWe found severity-related signatures in patient tissues mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

Invasive meningococcal disease (IMD) is a major public health concern because of its high case fatality, long-term morbidity, and potential to course with outbreaks. IMD caused by Nesseira meningitidis serogroup B has been predominant in different regions of the world like Europe and only recently broadly protective vaccines against B serogroup have become available. Two protein-based vaccines, namely 4CMenB (Bexsero®) and rLP2086 (Trumenba®) are currently licensed for use in different countries against MenB disease. These vaccines came from a novel technology on vaccine design (or antigen selection) using highly specific antigen targets identified through whole-genome sequence analysis. Moreover, it has the potential to confer protection against non-B meningococcus and against other Neisserial species such as gonococcus. Real-world data on the vaccine-use are rapidly accumulating from the UK and other countries which used the vaccine for control of outbreak or as part of routine immunization program, reiterating its safety and efficacy. Additional data on real-life effectiveness, long-term immunity, and eventual herd effects, including estimates on vaccine impact for cost-effectiveness assessment are further needed. Given the predominance of MenB in Europe and other parts of the world, these new vaccines are crucial for the prevention and public health control of the disease, and should be considered.

The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10−4; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10−5; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.

The introduction of pneumococcal conjugate vaccines (PCVs) in the routine immunization program has resulted in a significant decline in invasive pneumococcal diseases (IPD) around the world. Preterm infants are a special group at a high risk of invasive infection by encapsulated bacteria. However, their slow growth accrual and prolonged hospital stay frequently lead to delays in immunization, which contributes to their risk for severe infections. Areas covered: Authors reviewed the published immunogenicity and safety of the use of PCVs in preterm infants. Expert opinion: PCVs are safe and effective for use in low birth weight and in-hospital preterm infants. Local and systemic reactions are similar for both term and preterm populations. Reports were inconsistent on the risk of apnea, therefore hospitalized extremely premature infants should be kept under observation for at least 48 h after immunization.

The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an “iceberg” model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs. This work was supported by grants from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER (AS) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (FMT); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007-2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I (FMT), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021) (AS and FMT) SI

Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the practical prevention guide for CAP through vaccination in Spain developed in 2016 and updated in 2018, based on available vaccines and evidence through bibliographic review and expert opinion. The arrival of COVID-19 as a new cause of CAP and the recent availability of safe and effective vaccines constitutes the most significant change. Vaccines against pneumococcus, influenza, pertussis and COVID-19 can help to reduce the burden of disease from CAP and its associated complications. The available evidence supports the priority indications established in this guide, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice.

Monitoring adverse reactions following immunisation is essential, particularly for new vaccines such as those against COVID-19. We describe 20 cases of acute onset of a single supraclavicular lymphadenopathy manifesting between 24 h and 9 days after ipsilateral intramuscular administration of an mRNA-based COVID-19 vaccine, referred to our WHO Collaborating Centre for Vaccine Safety. Our results indicate that the swelling of supraclavicular lymph nodes following immunisation may constitute a benign and self-limited condition, related to a higher than recommended injection site.

Contains fulltext : 231542.pdf (Publisher’s version ) (Closed access) BACKGROUND: Respiratory tract infections (RTIs) are common in children with febrile illness visiting the general practitioner (GP) or emergency department. We studied the management of children with fever and RTI at 3 different levels of healthcare in The Netherlands, focusing on antibiotic prescription. METHODS: This prospective observational study is part of the Management and Outcome of Febrile children in Europe study. Data were used from face-to-face patient contacts of children with febrile illness in three healthcare settings in Nijmegen, The Netherlands during 2017. These settings were primary (GP), secondary (general hospital) and tertiary care (university hospital). RESULTS: Of 892 cases with RTI without complex comorbidities, overall antibiotic prescription rates were 29% with no differences between the 3 levels of healthcare, leading to an absolute number of 5031 prescriptions per 100,000 children per year in primary care compared with 146 in secondary and tertiary care combined. The prescription rate in otitis media was similar in all levels: 60%. In cases with lower RTI who received nebulizations prescription rates varied between 19% and 55%. CONCLUSIONS: Antibiotic prescription rates for RTIs in children were comparable between the 3 levels of healthcare, thus leading to a majority of antibiotics being prescribed in primary care. Relatively high prescription rates for all foci of RTIs were found, which was not in agreement with the national guidelines. Antibiotic stewardship needs improvement at all 3 levels of healthcare. Guidelines to prescribe small spectrum antibiotics for RTIs need to be better implemented in hospital care settings.

Background: The Bacillus Calmette-Guerin (BCG), the only vaccine against tuberculosis (TB) currently in use, has shown beneficial effects against unrelated infections and to enhance immune responses to vaccines. However, there is little evidence regarding the influence of BCG vaccination on pertussis. Methods: Here, we studied the ability of BCG to improve the immune responses to diphtheria, tetanus, and acellular (DTaP) or whole-cell pertussis (DTwP) vaccination in a mouse model. We included MTBVAC, an experimental live-attenuated vaccine derived from Mycobacterium tuberculosis, in our studies to explore if it presents similar heterologous immunity as BCG. Furthermore, we explored the potential effect of routine BCG vaccination on pertussis incidence worldwide. Findings: We found that both BCG and MTBVAC when administered before DTaP, triggered Th1 immune responses against diphtheria, tetanus, and pertussis in mice. Immunization with DTaP alone failed to trigger a Th1 response, as measured by the production of IFN-γ. Humoral responses against DTaP antigens were also enhanced by previous immunization with BCG or MTBVAC. Furthermore, exploration of human epidemiological data showed that pertussis incidence was 10-fold lower in countries that use DTaP and BCG compared to countries that use only DTaP. Interpretation: BCG vaccination may have a beneficial impact on the protection against pertussis conferred by DTaP. Further randomized controlled trials are needed to properly define the impact of BCG on pertussis incidence in a controlled setting. This could be a major finding that would support changes in immunization policies. Funding: This work was supported by the Ministry of “Economia y Competitividad”; European Commission H2020 program, “Gobierno de Aragon”; CIBERES; “Fundacao Butantan”; Instituto de Salud Carlos III and “Fondo FEDER”.

Objectives: To evaluate electrocardiogram markers to predict coronary involvement in patients with Kawasaki disease by assessing measures of ventricular repolarization parameters on the 12-lead electrocardiogram. Study design: This cross-sectional study included 180 Spanish and Japanese patients ≤14 years of age with Kawasaki disease, with or without coronary involvement, from 2011 to 2016. We manually measured the Tp-Te/QT ratio and QTc interval (with Bazett's formula) in 12-lead electrocardiogram in the acute and recovery period and explored their potential association with coronary involvement. Results: No association was found between Tp-Te/QT ratio obtained manually in V5 and V6 leads and coronary involvement in the acute (V5:0.25 [IQR, 0.21-0.27] vs 0.25 [IQR, 0.20-0.27], P = .80; V6:0.24 [IQR, 0.21-0.27] vs 0.25 [IQR, 0.20-0.27], P = .86) or the recovery (V5: 0.23 [IQR, 0.20-0.25] vs 0.23 [IQR, 0.19-0.25], P = .68; V6: 0.23 [IQR, 0.20-0.25] vs 0.23 [IQR, 0.17-0.25], P = .50) period. By contrast, QTc in V5 and V6 was significantly lower in patients with Kawasaki disease and coronary involvement in the acute period (V5: 378 ms [IQR, 364-395 ms] vs 390 ms [IQR, 371-411 ms], P = .04; V6: 377 ms [IQR, 364-392 ms] vs 390 ms [IQR, 371-410 ms], P = .01). A QTc interval of