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Background: Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at‐risk populations. This study is aimed at assessing hospital burden and healthcare resource utilization (HRU) of RSV and influenza in adults in Spain. Methods: Data were obtained from the Projected Hospitalisation Database of inpatient episodes (ages: younger adults 18–50 and 51–64 years; older adults 65–74, 75–84, and ≥ 85 years) during 2015, 2017, and 2018 in Spanish public hospitals. Incidence, mean hospitalization, and HRU assessments, including length of stay (LOS), intensive care unit (ICU) usage, and age‐standardized mortality rates, were collected and stratified by age group, with analyses focusing on the adult population (≥ 18 years old). Results: Mean hospitalization rate in the population across all years was lower in individuals with RSV versus influenza (7.2/100,000 vs. 49.7/100,000 individuals). ICU admissions and median LOS were similar by age group for both viruses. Age‐standardized mortality was 6.3/100,000 individuals and 6.1/100,000 individuals in patients with RSV and influenza, respectively, and mortality rates were similar in older adults (≥ 65 years) for both viruses. Conclusions: RSV and influenza infection were associated with considerable HRU. There is a substantial disease burden for RSV infection in older adults ≥ 65 years. While RSV hospitalization rates in adults reported here appeared lower than influenza, RSV is still underdiagnosed in the hospital setting and its incidence might be similar to, or higher than, influenza. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has pushed many healthcare systems into crisis. High vaccine coverage amongst children reduces emergency room presentations, hospital admissions and deaths due to vaccine-preventable diseases, freeing up healthcare resources including polymerase chain reaction testing for patients with SARS-CoV-2. In Europe, rotavirus gastroenteritis leads to 75,000–150,000 hospitalisations and up to 600,000 medical encounters annually. Nevertheless, in 2022, only 18 countries in Europe (out of 38) have a publicly funded routine universal mass immunisation programme against rotavirus gastroenteritis. Evidence available in the last few years re-emphasises that rotavirus vaccines currently available in Europe are highly effective, preventing up to 96% of rotavirus-related hospitalisations in children less than 1 year of age (potentially 72,000–144,000 hospitalisations Europe-wide). Long-term surveillance indicates that rotavirus vaccination does not result in an overall increase in intussusception. On the contrary, increasing evidence suggests an overall reduction in intussusception in the first 12 months of life when early, high rotavirus vaccine coverage is achieved. Prevention of rotavirus gastroenteritis has marked positive impacts on parental wages and government tax revenue, with benefits extending across the whole economy. In the SARS-CoV-2 pandemic setting there is a new imperative to achieve high levels of paediatric vaccination against vaccine-preventable diseases, including rotavirus gastroenteritis. The introduction of rotavirus universal mass vaccination can be expected to reduce the number of preventable illnesses, hospitalisations and deaths caused by rotavirus gastroenteritis. Reducing vaccine-preventable diseases is particularly urgent at this time when healthcare systems are preoccupied and overwhelmed with SARS-CoV-2. Graphical abstract available for this article. [ABSTRACT FROM AUTHOR]

Introduction: Immunization is the most effective strategy for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB); however, parents need to weigh the risk–benefit and financial impact of immunizing their children against MenB in the absence of a national immunization program (NIP). This study aimed to explore societal preferences (of parents and pediatricians) regarding the attributes of a MenB vaccine in Spain. Methods: A discrete choice experiment (DCE) based on cross-sectional surveys was carried out to determine preferences. A literature review and scientific committee determined the six attributes related to the MenB vaccine included in the DCE: vaccination age, cost, duration, percentage of protection, adverse events probability, and expert/authority recommendation. Data were analyzed using a mixed logit model. Relative importance (RI) of attributes was calculated and compared between parents and pediatricians. Results: A total of 278 parents [55.8% female, mean age 40.4 (standard deviation, SD 7.3) years] and 200 pediatricians [73.0% female, mean age 45.8 (SD 12.9) years] answered the DCE. For parents, the highest RI was attributed to vaccine cost, expert/authority recommendation, and percentage of protection (26.4%, 26.1%, and 22.9%, respectively), while for pediatricians the highest RI was assigned to percentage of protection, expert/authority recommendation, and vaccination age (27.2%, 23.7%, and 22.6%, respectively). Significant differences between parents and pediatricians were found in the RI assigned to all attributes (p < 0.001), except for vaccine recommendation. Conclusion: In the decision regarding MenB vaccination, cost was a driver in parental decision-making but had a low RI for pediatricians and, conversely, vaccination age was highly valued by pediatricians but was the attribute with least importance for parents. Despite these differences, expert/authority recommendation and percentage of protection were essential criteria for both groups. These results provide relevant information about MenB vaccination, highlighting the importance of considering societal preferences for NIP inclusion. [ABSTRACT FROM AUTHOR]

• Toddlers in a randomized maternal Tdap immunization trial received a DTaP-HepB-IPV/Hib booster. • Response to pertussis and to other antigens were similarly high in toddlers from vaccinated and unvaccinated mothers. • Antibody concentrations for two pertussis antigens and diphtheria were lower in toddlers from vaccinated mothers. • The clinical significance of this immune interference needs long-term monitoring. Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/ Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929. [ABSTRACT FROM AUTHOR]

Background This phase 1b study evaluated the pharmacokinetics, safety, and antiviral effects of the respiratory syncytial virus (RSV)–specific fusion inhibitor JNJ-53718678 (JNJ-8678) in hospitalized RSV-infected patients aged > 1 to ≤24 months. Methods Patients categorized by age (cohort 1: ≥6 to ≤24 months; cohort 2: ≥3 to < 6 months; cohort 3: > 1 to < 3 months) were randomized to oral JNJ-8678 or placebo once daily for 7 days. Dose increases followed data review committee recommendations (cohort 1: 2/6/8/9 mg/kg; cohort 2: 1.5/4.5/6 mg/kg; cohort 3: 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures were not reached at lower doses. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modeling. Safety was assessed by adverse events (AEs), laboratory tests, and electrocardiograms. To assess antiviral effects, RSV RNA viral load from nasal swabs was quantified over time using reverse-transcription quantitative polymerase chain reaction. Results Patients received JNJ-8678 (n = 37) or placebo (n = 7). Pharmacokinetic parameters were similar at the highest doses for cohorts 1–3 (area under the plasma concentration–time curve from time of administration up to 24 hours postdosing at day 7: 35 840, 34 980, and 39 627 ng × hour/mL, respectively). Two grade 3 AEs were reported (both bronchiolitis; 1 JNJ-8678, 1 placebo), reported as serious AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported (rhinitis [JNJ-8678]; pneumonia [placebo]). No deaths, grade 4 AEs, or AEs leading to discontinuation were reported. Median RSV viral load change from baseline in JNJ-8678 vs placebo by day 3 was −1.98 vs −0.32 log10 copies/mL. Conclusions In RSV-infected infants, JNJ-8678 was well tolerated. Target exposures were reached and antiviral activity was observed. Clinical Trials Registration NCT02593851. [ABSTRACT FROM AUTHOR]

The ReSVinet Scale is a clinical score for the assessment of respiratory difficulty in infancy. Our aim was to provide an update on the characteristics that make this tool different to any other. We descriptively compared the characteristics of the ReSVinet Scale with other options that can be found in the current literature or mobile apps stores. The ReSVinet Scale has been devised for its use regardless of the age of the child, entity causing respiratory symptoms, and setting. To this date, it is the only pediatric respiratory scale for acute respiratory distress that provides a parental version, and it is also the first one to have undergone validation in primary care. The tool can be found either in paper format or can be downloaded via App stores for devices running on Android or iOS systems. It has also been adopted recently as the assessment instrument for several clinical trials and for an IMI2 initiative (RESCEU project). All the aforementioned characteristics of the ReSVinet Scale should help toward its dissemination, as currently no other clinical tool for the assessment of respiratory difficulty can offer those advantages. [ABSTRACT FROM AUTHOR]

BACKGROUND: The capsular group B meningococcal vaccine (4CMenB) is recommended for children with complement deficiencies, asplenia, and splenic dysfunction; however, data on the immunogenicity of 4CMenB in these "at-risk" children are missing. METHODS: Participants aged 2 to 17 years in Italy, Spain, Poland, the United Kingdom, and Russia with complement deficiencies, asplenia, or splenic dysfunction received 2 doses of 4CMenB 2 months apart, as did healthy children in the control group. Exogenous and endogenous human complement serum bactericidal activity (SBA) was determined at baseline and 1 month after the second immunization against 4 test strains: H44/76 (assessing vaccine antigen factor H binding protein), 5/99 (Neisserial adhesion A), NZ98/254 (Porin A), and M10713 (Neisserial heparin binding antigen). RESULTS: Of 239 participants (mean age 10.3 years, 45% female), 40 children were complement deficient (9 eculizumab therapy, 4 terminal-chain deficiencies, 27 "other"), 112 children had asplenia or splenic dysfunction (8 congenital asplenia, 8 functional asplenia, 96 splenectomy), and 87 children were in the control group. After immunization, the proportions of complement-deficient participants with exogenous complement SBA titers ≥1:5 were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713), compared with 97%, 100%, 86%, and 94%, respectively, for asplenic children and 98%, 99%, 83%, and 99% for children in the control group. When testing with endogenous complement, strain-specific bactericidal activity was evident in only 1 eculizumab-treated participant and 1 terminal chain complement-deficient participant. CONCLUSIONS: 4CMenB administration is similarly immunogenic in healthy children and those with asplenia or splenic dysfunction. The significance of the trend to lower responses of SBA titers in complement-deficient children (especially those with terminal chain complement deficiency or those on eculizumab therapy) must be determined by ongoing surveillance for vaccine failures. [ABSTRACT FROM AUTHOR]

The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit–risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence. [ABSTRACT FROM AUTHOR]

DTaP5-IPV-HB-Hib vaccine is a fully-liquid, combination hexavalent vaccine. This phase III, open-label, multicentre study conducted in Spain, evaluated the immune response to all DTaP5-IPV-HB-Hib antigens when the vaccine was used in a mixed hexa/penta/hexa primary series. Infants (who had received one dose of hepatitis B vaccine at birth) received a mixed schedule including DTaP5-IPV-HB-Hib (PRP-OMP conjugate) at 2 and 6 months of age, DTaP5-IPV-Hib at 4 months, meningococcal serogroup C conjugate (MCC) vaccine at 2 and 4 months, and routine rotavirus and pneumococcal vaccination. One month post-dose 3 of the mixed schedule, response rates were considered acceptable if the lower bound of the two-sided 95% confidence interval around the post-vaccination response rate was >90% for hepatitis B and >80% for Haemophilus influenzae type b (Hib). Secondary immunogenicity objectives included description of the antibody response to all hexavalent antigens one month after completion of the mixed schedule, and to MCC antigen one month after the second MCC dose. The safety profile after each dose of study vaccine was described. Of 385 healthy infants enrolled, 384 completed the study. The primary objective was achieved for both hepatitis B and Hib; the lower bound of the 2-sided 95% CI of the response rates (97.2% and 99.0%, respectively) were greater than the pre-specified acceptability thresholds. One month post-dose 3 of the mixed schedule, all participants were seroprotected against diphtheria, tetanus and polio. The mixed schedule induced a robust immune response to all hexavalent antigens. The co-administration of the hexavalent vaccine in a mixed schedule with MCC vaccine did not reduce the immune response to vaccine antigens. Vaccines were well tolerated. In conclusion, the acceptability of response rates against Hib and hepatitis B were demonstrated one month post-dose 3 of the mixed schedule; robust immune responses against all other hexavalent antigens were observed. clinicaltrial.gov: NCT01839188 ; EudraCT: 2012-004221-25 [ABSTRACT FROM AUTHOR]

Background This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. Methods In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2 + 1 doses at 3½–5–11 months or 6–8–11 months of age, 3 + 1 doses at ages 2½–3½–5–11 months. Children aged 2–10 years received 2 catch-up doses administered 2 months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2 + 1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1 month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7 days post-vaccination; serious adverse events (SAEs) throughout the study. Results 754 infants and 404 children were enrolled. Post-primary vaccination, 98–100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48–77% for NHBA. Sufficiency of immune responses in infants receiving 2 + 1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95–99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. Conclusion Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. Funding GlaxoSmithKline Biologicals SA. [ABSTRACT FROM AUTHOR]

Having a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza's impact. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants. METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine). RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration ≥0.35 µg/mL for all serotypes: >85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and >97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups. CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization-established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age. [ABSTRACT FROM AUTHOR]

Background There is a growing interest among geneticists in developing panels of Ancestry Informative Markers (AIMs) aimed at measuring the biogeographical ancestry of individual genomes. The efficiency of these panels is commonly tested empirically by contrasting self-reported ancestry with the ancestry estimated from these panels. Results Using SNP data from HapMap we carried out a simulation-based study aimed at measuring the effect of SNP coverage on the estimation of genome ancestry. For three of the main continental groups (Africans, East Asians, Europeans) ancestry was first estimated using the whole HapMap SNP database as a proxy for global genome ancestry; these estimates were subsequently compared to those obtained from pre-designed AIM panels. Panels that consider >400 AIMs capture genome ancestry reasonably well, while those containing a few dozen AIMs show a large variability in ancestry estimates. Curiously, 500-1,000 SNPs selected at random from the genome provide an unbiased estimate of genome ancestry and perform as well as any AIM panel of similar size. In simulated scenarios of population admixture, panels containing few AIMs also show important deficiencies to measure genome ancestry. Conclusions The results indicate that the ability to estimate genome ancestry is strongly dependent on the number of AIMs used, and not primarily on their individual informativeness. Caution should be taken when making individual (medical, forensic, or anthropological) inferences based on AIMs. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study, which assessed the indirect economic impact of acute gastroenteritis induced by rotavirus in infants from a Galician area. The study also compared this with the burden due to acute gastroenteritis from other causes. Several factors analyzed in the study included work, travel, caregiver, meals, and materials.

What is the actual impact of music on the human being and the scope for scientific research in this realm? Compared to other areas, the study of the relationship between music and human biology has received limited attention. At the same time, evidence of music's value in clinical science, neuroscience, and social science keeps increasing. This review article synthesizes the existing knowledge of genetics related to music. While the success of genomics has been demonstrated in medical research, with thousands of genes that cause inherited diseases or a predisposition to multifactorial disorders identified, much less attention has been paid to other human traits. We argue for the development of a new discipline, sensogenomics, aimed at investigating the impact of the sensorial input on gene expression and taking advantage of new, discovery-based 'omic' approaches that allow for the exploration of the whole transcriptome of individuals under controlled experiments and circumstances. [ABSTRACT FROM AUTHOR]

Clinicians in Spain perceive an increase in the incidence of pediatric empyema. The available objective information is limited because it is a condition, for which there is no specific active epidemiological surveillance. This study aims to determine and evaluate the incidence of empyema of infectious origin, especially pneumococcal empyema, among children in Galicia (North-West of Spain). A retrospective search of all pediatrics cases of empyema from 1996 to present (May 2006) in Galicia (North-West of Spain) was performed using the official hospital admissions database. A total of 165 patients were identified, showing an increase in the incidence of empyema (1.02 cases/100,000 children in 1996 to 7.35 cases/100,000 children in 2005) and a decrease in the mean age of the patients affected [(7.25 (6.3) years in 1996 to 3.7 (3) in 2005]. This increase in the incidence of empyema started before the antipneumococcal vaccine became available and the reason for it remains unknown. This situation would justify the establishment of prospective systems for the surveillance and control of empyema. [ABSTRACT FROM AUTHOR]

Objective: To assess clinically the efficacy of vecuronium in providing prolonged muscle relaxation in children and to study the mean effective dose and its relation to patient age and duration of infusion. Design: Prospective, observational study. Setting: Pediatric intensive care unit (PICU) of a university tertiary care center. Patients: All pediatric patients consecutively admitted to our PICU between September 1998 and June 1999 requiring neuromuscular blockade for a period longer than 24 hours were included. Those with impairment of renal, liver and/or neuromuscular function were excluded from the study. Vecuronium infusion was adjusted according to clinically effective neuromuscular degree of blockade assessed by means of peripheral nerve stimulation in train-of-four (TOF) modality. Measurements and main results: Twenty patients were studied. Initial infusion rate was 0.09±0.01 mg/kg/hour. Duration of infusion ranged between 1 and 24 days. Mean infusion rate was 0.11±0.03 mg/kg/hour. Mean infusion rate of patients <2 years (0.085±0.016 mg/kg/hour) was significantly lower (p<0.001) than in older patients (0.133±0.030 mg/kg/hour). A significant positive correlation between age and mean infusion rate was detected (r =0.62, p =0.034). No correlation between mean doses and time of infusion was found. The most frequent adverse effect detected was peripheral edema (20%), always in patients ≤6 months old. Persistent quadriplegic myopathy was detected in a 13-year-old boy with status asthmaticus simultaneously treated with high doses of methylprednisolone. Conclusions: The clinically effective mean dose of vecuronium infusion varies according to age; the mean effective dose in children aged less than 2 years is a 36% minor than older patients'. When used for prolonged time, vecuronium infusion rate should be adjusted according to bedside neuromuscular function monitoring with peripheral nerve stimulation in TOF mode, in order to optimize degree of blockade and avoid overdosing and development of tolerance. The most frequent adverse effect in infants was peripheral edema. [ABSTRACT FROM AUTHOR]

The article presents a case study which evaluates a new meningococcal B (MenB) vaccine in Great Britain by the Joint Committee on Vaccination and Immunization (JCVI). Topics include introduction of MenB vaccine (Bexsero) for infant immunisation, impact and cost effectiveness of possible immunisation strategies, and methodology of Great Britain's the National Institute for Health and Care Excellence (NICE) adopted by JCVI to assess cost effectiveness of vaccine.

Background: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short‐ to mid‐term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population‐based cohort approach. Methods: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non‐hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow‐up period were undertaken. We defined mid‐term outcomes as those taking place up to 24 months of follow‐up period. Results: The study included 6626 children (3313 RSV‐hospitalized; 3313 non‐hospitalized) with a median follow‐up of 53.7 months (IQR = 27.9, 69.4). After a 3‐month follow‐up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84–4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34–5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93–7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96–2.05), nurse (IRR = 1.89, 95% CI: 1.75–1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17–2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31–1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43–6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38–4.81). All findings remained substantial until 2 years of post‐infection. Conclusions: Severe RSV infection in infants significantly increases short‐ to mid‐term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost‐effectiveness of RSV prevention programs. [ABSTRACT FROM AUTHOR]

Describes three girls with isolated external genitalia anomalies consisting of clitoral agenesis and lack of one or both labia minora. Features of the patients; Explanation for the genital anomalies.

Background Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide. Most children experience at least one 1 RSV infection by the age of two 2 years, but not all develop severe disease. However, the understanding of genetic risk factors for severe RSV is incomplete. Consequently, we conducted a genome-wide association study of RSV severity. Methods Disease severity was assessed by the ReSVinet scale, in a cohort of 251 infants aged 1 week to 1 year. Genotyping data were collected from multiple European study sites as part of the RESCEU Consortium. Linear regression models were used to assess the impact of genotype on RSV severity and gene expression as measured by microarray. Results While no SNPs reached the genome-wide statistical significance threshold (P < 5 × 10−8), we identified 816 candidate SNPs with a P -value of <1 × 10−4. Functional annotation of candidate SNPs highlighted genes relevant to neutrophil trafficking and cytoskeletal functions, including LSP1 and RAB27A. Moreover, SNPs within the RAB27A locus significantly altered gene expression (false discovery rate, FDR P <.05). Conclusions These findings may provide insights into genetic mechanisms driving severe RSV infection, offering biologically relevant information for future investigations. [ABSTRACT FROM AUTHOR]

Background During the first year of life, 1 in 4 infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV therefore underrepresents the true societal burden of RSV. We assessed the burden of nonmedically attended RSV infections and compared with medically attended RSV. Methods We performed active RSV surveillance until the age of 1 year in a cohort (n = 993) nested within the Respiratory Syncytial Virus Consortium in EUrope (RESCEU) prospective birth cohort study enrolling healthy term-born infants in 5 European countries. Symptoms, medication use, wheezing, and impact on family life were analyzed. Results For 97 of 120 (80.1%) nonmedically attended RSV episodes, sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97) of episodes; worries, 75.3% (73/97); anxiety, 34.0% (33/97); and work absenteeism, 10.8% (10/93). Compared with medically attended RSV (n = 102, 9 hospital admissions), Respiratory Syncytial Virus NETwork (ReSViNET) severity scores were lower (3.5 vs 4.6, P <.001), whereas duration of respiratory symptoms and was comparable. Conclusions Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families, and society. These findings are important for policy makers when considering the implementation of RSV immunization. Clinical Trials Registration. ClinicalTrials.gov (NCT03627572). [ABSTRACT FROM AUTHOR]

Background There is no consensus on how to best quantify disease severity in infants with respiratory syncytial virus (RSV) and/or bronchiolitis; this lack of a sufficiently validated score complicates the provision of clinical care and, the evaluation of trials of therapeutics and vaccines. The ReSVinet score appears to be one of the most promising; however, it is too time consuming to be incorporated into routine clinical care. We aimed to develop and externally validate simplified versions of this score. Methods Data from a multinational (the Netherlands, Spain, and United Kingdom) multicenter case-control study of infants with RSV were used to develop simplified versions of the ReSVinet score by conducting a grid search to determine the best combination of equally weighted parameters to maximize for the discriminative ability (measured by area under the receiver operating characteristic curve [AUROC]) across a range of outcomes (hospitalization, intensive care unit admission, ventilation requirement). Subsequently discriminative validity of the score for a range of secondary care outcomes was externally validated by secondary analysis of datasets from Rwanda and Colombia. Results Three candidate simplified scores were identified using the development dataset; they were excellent (AUROC >0.9) at discriminating for a range of outcomes, and their performance was not significantly different from the original ReSVinet score despite having fewer parameters. In the external validation datasets, the simplified scores were moderate to excellent (AUROC, 0.7–1) across a range of outcomes. In all outcomes, except in a single dataset for predicting admission to the high-dependency unit, they performed at least as well as the original ReSVinet score. Conclusions The candidate simplified scores developed require further external validation in larger datasets, ideally from resource-limited settings before any recommendation regarding their use. [ABSTRACT FROM AUTHOR]

Background Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. Methods Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final "bacterial" or "viral" phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. Results Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/β-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the "Watch" category. Conclusions Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics. A significant proportion of patients with a viral phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology could significantly improve antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. Methods Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. Results Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post–ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post–dose 2. Conclusions ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration.  NCT03636906. [ABSTRACT FROM AUTHOR]

Whereas most infants infected with respiratory syncytial virus (RSV) show no or only mild symptoms, an estimated 3 million children under five are hospitalized annually due to RSV disease. This study aimed to investigate biological mechanisms and associated biomarkers underlying RSV disease heterogeneity in young infants, enabling the potential to objectively categorize RSV‐infected infants according to their medical needs. Immunophenotypic and functional profiling demonstrated the emergence of immature and progenitor‐like neutrophils, proliferative monocytes (HLA‐DRLow, Ki67+), impaired antigen‐presenting function, downregulation of T cell response and low abundance of HLA‐DRLow B cells in severe RSV disease. HLA‐DRLow monocytes were found as a hallmark of RSV‐infected infants requiring hospitalization. Complementary transcriptomics identified genes associated with disease severity and pointed to the emergency myelopoiesis response. These results shed new light on mechanisms underlying the pathogenesis and development of severe RSV disease and identified potential new candidate biomarkers for patient stratification. [ABSTRACT FROM AUTHOR]

Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n = 60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD) as revealed by a multi-cohort study (n = 1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than in controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders. [ABSTRACT FROM AUTHOR]

Background: Studies on vaccine effectiveness (VE) against COVID‐19 in the pediatric population are outgoing. We aimed to quantify VE against SARS‐CoV‐2 in two pediatric age groups, 5–11 and 12–17‐year‐old, while considering vaccine type, SARS‐CoV‐2 variant, and duration of protection. Methods: A population‐based test‐negative control study was undertaken in Galicia, Spain. Children 5–11‐year‐old received the Comirnaty® (Pfizer, US) vaccine, while those aged 12–17‐year‐old received the Comirnaty® (Pfizer, US) or SpikeVax® (ModernaTX, Inc) vaccine. Participants were categorized into unvaccinated (0 doses or one dose with <14 days since vaccination), partially vaccinated (only one dose with ≥14 days, or two doses with <14 days after the second dose administration), and fully vaccinated (two doses with ≥14 days after the second injection). Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated using multiple logistic regression models. VE was calculated as (1‐OR) * 100. Stratified and sensitivity analyses were performed. Results: In the fully vaccinated 5–11‐year‐old children, VE against the Omicron variant was 44.1% (95% CI: 38.2%–49.4%). In the fully vaccinated 12–17‐year‐old individuals, VE was 83.4% (95% CI: 81.2%–85.3%) against Delta and 74.8% (95% CI: 58.5%–84.9%) against Omicron. Comirnaty® and SpikeVax® vaccines showed a similar magnitude of VE against Delta [Comirnaty® VE: 81.9% (95% CI: 79.3%–84.1%) and SpikeVax® VE: 85.3% (95% CI: 81.9%–88.1%)]. Comirnaty® (Pfizer, US; VE: 79.7%; 95% CI: 50.7%–92.4%) showed a slightly higher magnitude of protection against Omicron than SpikeVax® (ModernaTX, Inc), yet with an overlapping CI (VE: 74.3%; 95% CI: 56.6%–84.9%). VE was maintained in all age subgroups in both pediatric populations, but it declined over time. Conclusions: In Galicia, mRNA VE was moderate against SARS‐CoV‐2 infections in the 5–11‐year‐old populations, but high in older children. VE declined over time, suggesting a potential need for booster dose schedules. [ABSTRACT FROM AUTHOR]

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the decision of the Spanish Agency on Drugs and Health Products to restrict the use of 4CMenB vaccine to hospital use only, until specifications of its use are established, despite the approval by the European Medical Agency.

Background Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12–23-month-old RSV-seropositive children followed up for 2 years after vaccination. Methods Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti–RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2. Results Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1. Conclusions Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. Clinical Trials Registration NCT02927873. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Invasive pneumococcal disease, comorbidities, and polysaccharide vaccine use in children aged 5â€"15 years in England and Wales" by S.N. Ladhani and colleagues in a 2014 issue.

• We collected daily data to assess the impact of RSV on infants and caregivers. • RSV quality of life loss was substantial, irrespective of medical attendance. • The quality of life loss in a caregiver trailed that of their infant with RSV. • Costs varied by country and were negligible for non-medically attended RSV. Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs. [ABSTRACT FROM AUTHOR]

To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the 'Biomarker Validation in HR patients' database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population. What is Known: • Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom. • Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low. What is New: • Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective. • The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers. [ABSTRACT FROM AUTHOR]

Establishing the timeframe when a particular virus was circulating in a population could be useful in several areas of biomedical research, including microbiology and legal medicine. Using simulations, we demonstrate that the circulation timeframe of an unknown SARS-CoV-2 genome in a population (hereafter, estimated time of a queried genome [QG]; tE-QG) can be easily predicted using a phylogenetic model based on a robust reference genome database of the virus, and information on their sampling dates. We evaluate several phylogeny-based approaches, including modeling evolutionary (substitution) rates of the SARS-CoV-2 genome (~10−3 substitutions/nucleotide/year) and the mutational (substitutions) differences separating the QGs from the reference genomes (RGs) in the database. Owing to the mutational characteristics of the virus, the present Viral Molecular Clock Dating (VMCD) method covers timeframes going backwards from about a month in the past. The method has very low errors associated to the tE-QG estimates and narrow intervals of tE-QG, both ranging from a few days to a few weeks regardless of the mathematical model used. The SARS-CoV-2 model represents a proof of concept that can be extrapolated to any other microorganism, provided that a robust genome sequence database is available. Besides obvious applications in epidemiology and microbiology investigations, there are several contexts in forensic casework where estimating tE-QG could be useful, including estimation of the postmortem intervals (PMI) and the dating of samples stored in hospital settings. [ABSTRACT FROM AUTHOR]

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 (<3 months vs 3 to <6 months and 3 to <6 months vs ≥6 months). Older age (≥6 months vs <3 months), higher viral load, and RSV-A were associated with a greater probability of fever. RSV-A and RSV-B caused similar disease severity and had similar viral dynamics. Infants with a more severe RSV infection, demonstrated by having a higher ReSViNET score, fever, and requiring hospitalization and intensive care, were more likely to have developed subsequent wheezing at 1 year of age.Clinical Trials Registration: NCT03756766. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infections occur in human populations around the globe, causing disease of variable severity, disproportionately affecting infants and older adults (>65 years of age). Immune responses can be protective but also contribute to disease. Experimental studies in animals enable detailed investigation of immune responses, provide insights into clinical questions, and accelerate the development of passive and active vaccination. We aimed to review the role of antibody and T-cell responses in relation to RSV disease severity in animals.Methods: Systematic review and meta-analysis of animal studies examining the association between T-cell responses/phenotype or antibody titers and severity of RSV disease. The PubMed, Zoological Record, and Embase databases were screened from January 1980 to May 2018 to identify animal studies of RSV infection that assessed serum antibody titer or T lymphocytes with disease severity as an outcome. Sixty-three studies were included in the final review.Results: RSV-specific antibody appears to protect from disease in mice, but such an effect was less evident in bovine RSV. Strong T-cell, Th1, Th2, Th17, CD4/CD8 responses, and weak Treg responses accompany severe disease in mice.Conclusions: Murine studies suggest that measures of T-lymphocyte activity (particularly CD4 and CD8 T cells) may be predictive biomarkers of severity. Further inquiry is merited to validate these results and assess relevance as biomarkers for human disease. [ABSTRACT FROM AUTHOR]

Background. Bacille Calmette-Guerin (BCG) vaccination has been suggested to have nonspecific beneficial effects in children from developing countries, reducing morbidity and mortality caused by unrelated pathogens. Objective. We aimed to assess the heterologous protective effects of BCG vaccination against respiratory infection (RI) and sepsis not attributable to tuberculosis in children born in Spain. Methods. We conducted a retrospective epidemiological study using data from the Official Spanish Registry of Hospitalizations (CMBD-HA) to identify differences in hospitalization rates (HR) in BCG-vaccinated children (Basque Country, where neonatal BCG is part of the immunization schedule and has a 100% coverage) as compared to non-BCG-vaccinated children (from the rest of Spain, where BCG is not used). Results. A total of 464 611 hospitalization episodes from 1992 to 2011 were analyzed. The HR due to RI not attributable to tuberculosis in BCG-vaccinated children was significant lower compared to non-BCG-vaccinated children for all age groups, with a total preventive fraction (PF) of 41.4% (95% confidence interval: 40.3-42.5; Pvalue <.001). According to age group, PF was 32.4% (30.9-33.9; P-value <.001) for children under 1 year old, 60.1% (58.5-61.7; P-value <.001) for children between 1 and 4 years old, 66.6% (62.8-70.2; P-value <.001) for children between 5 and 9 years old, and 69.6% (63.3-75.0; P-value <.001) for children between 10 and 14 years old. The HR due to sepsis not attributable to tuberculosis in BCG-vaccinated children under 1 year of age was also significantly lower, with a PF of 52.8% (43.8-60.7; P-value <.001). Conclusions. BCG vaccination at birth may decrease hospitalization due to RI and sepsis not related to tuberculosis through heterologous protection. [ABSTRACT FROM AUTHOR]

Asbtract: BACKGROUND: Electronic vaccine registries are not yet widely established. There is a need to real-time monitor influenza vaccine coverage, which may raise awareness to risk groups and professionals, and eventually allow to adopt tailored measures during the vaccination campaign. To evaluate the utility of the "Gripómetro", a demographic study designed to monitor national and regional influenza vaccine coverage on a weekly basis in Spain.Methods: Quantitative study based on surveys of the Spanish population between 18-80 years and a sample of primary care doctors and nurses randomly selected. Pre-proportional fixation has been established by Autonomous Communities and age group to guarantee the representativeness of all the autonomies.Results: Interviews were conducted in 3400 households of general population and 807 respondents among health care professionals. We found that the results of influenza vaccination coverage in the population ≥ 65 years obtained by the Gripómetro for 2018-2019 season were mostly comparable with the official data presented by the Ministry of Health after the end of the vaccination campaign.Conclusions: The Gripómetro is a robust research method that provides real-time data and trends for influenza vaccine coverage along with other useful information related to vaccination such as intention to vaccinate, motivation and barriers to vaccination. [ABSTRACT FROM AUTHOR]

Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is challenging. By examining the largest database of SARS-CoV-2 genomes The Global Initiative on Sharing Avian Influenza Data [GISAID; n >1.2 million high-quality (HQ) sequences], we present evidence suggesting that superspreading has had a key role in the epidemiological predominance of VOC. There are clear signatures in the database compatible with large superspreading events (SSEs) coinciding chronologically with the worst epidemiological scenarios triggered by VOC. The data suggest that, without the randomness effect of the genetic drift facilitated by superspreading, new VOC of SARS-CoV-2 would have had more limited chance of success. Viral genome phylogenies reflect patterns of virus transmissions (e.g., signatures left by transmission chains differ from those left by superspreading). Due to an incubation time of ~5 to 6 days and an evolutionary rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the order of ~10–3, superspreading transmissions generate starlike phylogenies that find perfect parallelism in contact tracing networks. It is likely that thousands of variants of concern (VOC) passed unnoticed to genome databases because they have died out before having the opportunity to emerge in the population (or have not been sampled). Given that mutational changes occur in a nearly constant way, it is not obvious how to determine the mutation/s that make the virus more infectious. The algorithm of the pandemic is not simple and superspreading should be considered as one of the main catalyzers of the SARS-CoV-2 pandemic worldwide, independently of the viral variant involved. Evidence points to a key role of superspreading in the success of VOC. Studies analyzing selective forces on VOC should not ignore the power of genetic drift on spreading. [ABSTRACT FROM AUTHOR]

We and others have reported several genes that are differentially expressed in RSV-infected patients compared to healthy controls [[1]], as well as genetic variation of the host that might constitute increased susceptibility to RSV infection [[3]]. To theEditor - Host factors influence respiratory syncytial virus (RSV) susceptibility and course. We next examined transcription patterns in the I CD14 i gene showing a decreasing expression of I CD14 i from CR-RSV to RW-RSV and AS-RSV patients (Figure 1 I A i ). [Extracted from the article]

National Immunization Technical Advisory Groups are groups of multi-disciplinary experts that provide scientific advice to policy makers to enable them to make informed immunization policy and programme decisions. NITAGs faced challenges using their routine approach to develop recommendations for COVID-19 vaccines during the pandemic. In response, the WHO Regional Office for Europe (Regional Office), with the support of the Robert Koch Institute, developed an innovative approach of a series of webinars, provision of materials, and remote technical assistance to address these challenges. Polls conducted during webinars were used to tailor future webinars and evaluate the effectiveness of these interventions. According to poll results, 76% of participants found the webinars and resources shared very useful in their work on COVID-19 vaccination. The Regional Office plans to build further upon the scope of online communication and establish a regional online platform for NITAGs to further support NITAGs and build capacity. [ABSTRACT FROM AUTHOR]

Presents letters to the editor on medical topics as of March 1, 2002. Glutaric aciduria type one and non-accidental head injury; High-frequency oscillatory ventilation; Magnetic resonance imaging and kernicterus; Discussion of Staphylococcus aureus.

Unravelling the molecular mechanism of COVID-19 vaccines through transcriptomic pathways involved in the host response to SARS-CoV-2 infection is key to understand how vaccines work, and for the development of optimized COVID-19 vaccines that can prevent the emergence of SARS-CoV-2 variants of concern (VoCs) and future outbreaks. In this study, we investigated the effects of vaccination with a modified vaccinia virus Ankara (MVA)-based vector expressing the full-length SARS-CoV-2 spike protein (MVA-S) on the lung transcriptome from susceptible K18-hACE2 mice after SARS-CoV-2 infection. One dose of MVA-S regulated genes related to viral infection control, inflammation processes, T-cell response, cytokine production and IFN-γ signalling. Down-regulation of Rhcg and Tnfsf18 genes post-vaccination with one and two doses of MVA-S may represent a mechanism for controlling infection immunity and vaccine-induced protection. One dose of MVA-S provided partial protection with a distinct lung transcriptomic profile to healthy animals, while two doses of MVA-S fully protected against infection with a transcriptomic profile comparable to that of non-vaccinated healthy animals. This suggests that the MVA-S booster generates a robust and rapid antigen-specific immune response preventing virus infection. Notably, down-regulation of Atf3 and Zbtb16 genes in mice vaccinated with two doses of MVA-S may contribute to vaccine control of innate immune system and inflammation processes in the lungs during SARS-CoV-2 infection. This study shows host transcriptomic mechanisms likely involved in the MVA-S vaccine-mediated immune response against SARS-CoV-2 infection, which could help in improving vaccine dose assessment and developing novel, well-optimized SARS-CoV-2 vaccine candidates against prevalent or emerging VoCs. • One dose of MVA-S upregulates innate and adaptive genes in SARS-CoV-2 infected mice. • MVA-S booster inhibits immune genes and promotes antigen-specific T-cell responses. • Number of MVA-S doses affects T-cell response in the lungs and disease evolution. • MVA-S regulation of Atf3 and Zbtb16 may control innate immunity and inflammation. • Transcriptional profile of the MVA-S response to infection aids vaccine optimization. [ABSTRACT FROM AUTHOR]

Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, generalized approach to pathogen sequencing and transcriptome profiling. Using this method, we recovered 13 (76%) complete human respiratory syncytial virus (RSV) genomes from 17 clinical respiratory samples, reconstructed the phylogeny of the infecting viruses, and detected differential gene expression between 2 RSV subgroups, specifically, a lower expression of the P gene and a higher expression of the M2 gene in RSV-A than in RSV-B. This methodology can help to relate viral genetics to clinical phenotype and facilitate ongoing population-level RSV surveillance and vaccine development. Clinical Trials Registration. NCT03627572 and NCT03756766. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although prematurity and cardiopulmonary disease are risk factors for severe disease, the majority of infants hospitalized with RSV are previously healthy. Various vaccines and therapeutics are under development and expected to be available in the near future. To inform the use of these new vaccines and therapeutics, it is necessary to determine the burden of RSV disease in Europe. We will prospectively follow-up a birth cohort to obtain incidence data on RSV acute respiratory tract infection (ARTI).Methods: Multicenter prospective study of a birth cohort consisting of 10 000 healthy infants, recruited during 3 consecutive years. RSV associated hospitalization in the first year of life will be determined by questionnaires and hospital chart reviews. A nested cohort of 1000 infants will be actively followed. In case of ARTI, a respiratory sample will be collected for RSV molecular diagnosis.Results: The primary outcome is the incidence rate of RSV-associated hospitalization in the first year of life. In the active cohort the primary outcome is RSV associated ARTI and MA-ARTI.Conclusions: We will provide key information to fill the gaps in knowledge about the burden of RSV disease in healthy infants.Clinical Trials Registration: NCT03627572. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Early detection of RSV can optimize clinical management and minimize use of antibiotics. BinaxNOW RSV (BN) is a rapid antigen detection test that is widely used. We aimed to validate the sensitivity of BN in hospitalized and nonhospitalized infants against the gold standard of molecular diagnosis.Methods: We evaluated the performance of BN in infants with acute respiratory tract infections with different degrees of disease severity. Diagnostic accuracy of BN test results were compared with molecular diagnosis as reference standard.Results: One hundred sixty-two respiratory samples from 148 children from October 2017 to February 2019 were studied. Sixty-six (40.7%) samples tested positive for RSV (30 hospitalizations, 31 medically attended episodes not requiring hospitalization, and 5 nonmedically attended episodes). Five of these samples tested positive with BN, leading to an overall sensitivity of BN of 7.6% (95% confidence interval [CI], 3.3%-16.5%) and a specificity of 100% (95% CI, 96.2%-100%). Sensitivity was low in all subgroups.Conclusions: We found a low sensitivity of BN for point-of-care detection of RSV infection. BinaxNOW RSV should be used and interpreted with caution. [ABSTRACT FROM AUTHOR]

Purpose: Quadrivalent influenza vaccine (QIV) includes the same strains as trivalent influenza vaccine (TIV) plus an additional B strain of the other B lineage. The aim of the study was to analyse the public health and economic impact of replacing TIV with QIV in different scenarios in Spain. Methods: A dynamic transmission model was developed to estimate the number of influenza B cases prevented under TIV and QIV strategies (<65 years (high risk) and ≥65 years). This model considers cross-protective immunity induced by different lineages of influenza B. The output of the transmission model was used as input for a decision tree model that estimated the economic impact of switching TIV to QIV. The models were populated with Spanish data whenever possible. Deterministic univariate and probabilistic multivariate sensitivity analyses were performed. Results: Replacing TIV with QIV in all eligible patients with current vaccine coverage in Spain may have prevented 138,707 influenza B cases per season and, therefore avoided 10,748 outpatient visits, 3,179 hospitalizations and 192 deaths. The replacement could save €532,768 in outpatient visit costs, €13 million in hospitalization costs, and €3 million in costs of influenza-related deaths per year. An additional €5 million costs associated with productivity loss could be saved per year, from the societal perspective. The budget impact from societal perspective would be €6.5 million, and the incremental cost-effectiveness ratio (ICER) €1,527 per quality-adjusted life year (QALY). Sensitivity analyses showed robust results. In additional scenarios, QIV also showed an impact at public health level reducing influenza B related cases, outpatient visits, hospitalizations and deaths. Conclusions: Our results show public health and economic benefits for influenza prevention with QIV. It would be an efficient intervention for the Spanish National Health Service with major health benefits especially in the population ≥65-year. [ABSTRACT FROM AUTHOR]