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As it does every year, the CAV-AEP publishes the update of its recommendations for the use of vaccines in children, adolescents and pregnant women residing in Spain. The 2 + 1 schedule is maintained in infants (at 2, 4 and 11 months), including preterm infants, with the hexavalent vaccine (DTaP-IPV-Hib-HB) and the pneumococcal 13-valent conjugate vaccine. A booster dose with DTaP-IPV is needed at 6 years for those who received the 2 + 1 series with hexavalent vaccine as infants, in addition to 1 dose of dTap in adolescence. Routine vaccination of pregnant women with a dose of dTap is recommended in each pregnancy, preferably between weeks 27 and 32 of gestation, although can be given from 20 weeks if there is risk of preterm delivery. All infants should receive the rotavirus vaccine (2-3 doses) and the 4CMenB vaccine (2 + 1 series). All children aged 6-59 months should be vaccinated against influenza each year. The MenACWY vaccine should be given routinely at 12 months of age and in adolescence between ages 12 and 18 years. The recommendations for the MMR vaccine (12 months and 3-4 years) and varicella vaccine (15 months and 3-4 years) also remain unchanged, using the MMRV vaccine for the second dose. Recommendations for the use of SARS-CoV-2 vaccines in the paediatric age group will be updated periodically on the CAV-AEP website. The HPV vaccine is indicated in all adolescents, regardless of sex, at age 12 years. Novelties include the recommendation of routine administration of nirsevimab to neonates and infants aged less than 6 months for passive immunization against RSV, and the recommendations regarding the hexavalent vaccine are consolidated in a single section.

[Objectives]: To describe the etiology of community-acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology., [Hypothesis]: The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data., [Design]: Observational, multicenter, and prospective study., [Patient selection]: This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019., [Methods]: An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups., [Results]: Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para-pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens., [Conclusions]: Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient., Instituto de Investigación Hospital 12 de Octubre (i+12), Grant/Award Number: AY191212‐1; Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and co‐funded by the European Regional Development Funds, Grant/Award Number: Project PI17/01458; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Grant/Award Number: PCAPE 2011_0025 Register 320/11; Research Project of Universidad Europea de Madrid, Grant/Award Number: 2017/UEM03

After reviewing the best available scientific information, CAV-AEP publishes their new recommendations to protect pregnant women, children and adolescents living in Spain through vaccination.The same recommendations as the previous year regarding hexavalent vaccines, pneumococcal conjugate vaccine of 13 serotypes, booster with tetanus, diphtheria, pertussis and inactivated poliomyelitis (Tdpa-IPV) at 6 years and with tetanus, diphtheria and pertussis (Tdpa) at 12–14 years and pregnant women from week 27 (from week 20 if there is a high risk of preterm delivery).Also with rotavirus, tetraantigenic meningococcal B (2 + 1), meningococcal quadrivalent (MenACWY), MMR, varicella and human papillomavirus (HPV) vaccines, for both genders.As novelties this year the CAV-AEP recommends:Influenza vaccination from 6 to 59 months of age whenever feasible and does not harm the vaccination program aimed at people at higher risk.According to official national recommendations, the CAV-AEP recommends the systematic use of COVID mRNA vaccines since 5 years old. Resumen: Tras la revisión de la mejor información científica disponible, el CAV-AEP publica las nuevas recomendaciones para proteger con vacunas a las embarazadas, los niños y los adolescentes residentes en España.Se mantienen las mismas recomendaciones que el año anterior en cuanto a las vacunas hexavalentes y a la vacuna neumocócica conjugada de 13 serotipos, al refuerzo con tétanos, difteria, tosferina y poliomielitis inactivada (Tdpa-VPI) a los seis años y con tétanos, difteria y tosferina (Tdpa) a los 12-14 años y a las embarazadas a partir de la semana 27 (desde la semana 20 si hay alto riesgo de parto pretérmino).Lo mismo sucede con las vacunas del rotavirus, del meningococo B tetraantigénica (2 + 1), de la vacuna meningocócica tetravalente (MenACWY), de la triple vírica, de la varicela y de la vacuna del virus del papiloma humano (VPH), en ambos géneros.Como novedades este año el CAV-AEP recomienda:La vacunación antigripal de seis a 59 meses de edad siempre que sea factible y no perjudique al programa vacunal dirigido a las personas de mayor riesgo.En consonancia con las recomendaciones oficiales nacionales, el CAV-AEP recomienda el uso sistemático a partir de los 5 años de las vacunas para la COVID-19 de ARNm.

Background: Establishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. Most of the admitted children with CAP receive antibiotics. We aimed to build and validate a diagnostic tool combining clinical, analytical and radiographic features to differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria. Methods: Design-observational, multi-center, prospective cohort study was conducted in 2 phases. Settings: 24 secondary and tertiary hospitals in Spain. Patients-A total of 495 consecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. Interventions-A score with 2 sequential steps was built (training set, 70% patients, and validation set 30%). Step 1 differentiates between viral and bacterial CAP and step 2 between typical and atypical bacterial CAP. Optimal cutoff points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. Main outcome measures-Viral or bacterial etiology. Results: In total, 262 (53%) children (median age: 2 years, 52.3% male) had an etiologic diagnosis. In step 1, bacterial CAPs were classified with a sensitivity = 97%, a specificity = 48%, and a ROC's area under the curve = 0.81. If a patient with CAP was classified as bacterial, he/she was assessed with step 2. Typical bacteria were classified with a sensitivity = 100%, a specificity = 64% and area under the curve = 0.90. We implemented the score into a mobile app named Pneumonia Etiology Predictor, freely available at usual app stores, that provides the probability of each etiology. Conclusions: This 2-steps tool can facilitate the physician's decision to prescribe antibiotics without compromising patient safety. Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) Instituto de Investigacion Hospital 12 de Octubre (i+12) AY191212-1 Universidad Europea de Madrid 2017/UEM03 Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS) Spanish Government Grant for emerging groups (PCAPE 2011_0025; 320/11) 3.806 JCR (2021) Q1, 31/130 Pediatrics 1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child Health No data IDR 2021 UEM

We conducted a multicenter clinical validity study of the Panbio coronavirus disease 2019 Antigen Rapid Test of nasopharyngeal samples in pediatric patients with coronavirus disease 2019-compatible symptoms of ≤5 days of evolution. Our study showed limited accuracy in nasopharyngeal antigen testing: overall sensitivity was 45.4%, and 99.8% of specificity, positive-predictive value was 92.5%.

El CAV-AEP publica anualmente el calendario de vacunaciones que estima idóneo para los niños residentes en España, teniendo en cuenta la evidencia científica disponible. Se mantiene el esquema 2 + 1 (2, 4 y 11 meses) con vacunas hexavalentes (DTPa-VPI-Hib-HB) y con antineumocócica conjugada 13-valente. Se aconseja un refuerzo a los 6 años, preferentemente con DTPa (si está disponible), junto a una dosis de polio para aquellos que recibieron esquemas 2 + 1, así como vacunación con Tdpa en adolescentes y en cada embarazo, preferentemente entre las 27 y las 32 semanas. La vacuna del rotavirus debería ser sistemática para todos los lactantes. Se sigue proponiendo la incorporación en el calendario de la vacuna antimeningocócica B, con esquema 2 + 1 en lactantes. Además de la inclusión de la vacuna antimeningocócica conjugada tetravalente (MenACWY) a los 12 años con rescate hasta los 18 años, inclusive, el CAV recomienda que esta vacuna sea introducida también a los 12 meses de edad, sustituyendo a MenC. Igualmente, se recomienda en los mayores de 6 semanas de edad con factores de riesgo o que viajen a países de elevada incidencia de estos serogrupos. Se emplearán esquemas de 2 dosis para triple vírica (12 meses y 3-4 años) y varicela (15 meses y 3-4 años). La segunda dosis se podría aplicar como vacuna tetravírica. Se recomienda la vacunación sistemática universal frente al VPH, tanto a chicas como a chicos, preferentemente a los 12 años, debiendo realizar un mayor esfuerzo para mejorar las coberturas. La de 9 genotipos amplía la cobertura para ambos sexos, The CAV-AEP annually publishes the immunisation schedule considered optimal for all children resident in Spain, taking into account the available evidence. The 2 + 1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa- VPI-Hib-HB) and with 13-valent pneumococcal conjugate. A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2 + 1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, both for girls and boys, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children resident in Spain, taking into account the available evidence. The 2+1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate. A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2+1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, both for girls and boys, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders.

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children and adolescent resident in Spain, taking into account the available evidence.The 2 + 1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate. A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2 + 1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks.Rotavirus vaccine should be systematic for all infants.Meningococcal B vaccine, with a 2 + 1 schedule, should be included in routine calendar.In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups.Two-dose schedules for triple viral (12 months and 3–4 years) and varicella (15 months and 3–4 years) will be used. The second dose could be applied as a tetraviral vaccine.Universal systematic vaccination against HPV is recommended, regardless of gender, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders. Resumen: El CAV-AEP publica anualmente el calendario de vacunaciones que estima idóneo para los niños y adolescentes residentes en España, teniendo en cuenta la evidencia científica disponible.Se mantiene el esquema 2 + 1 (2, 4 y 11 meses) con vacunas hexavalentes (DTPa-VPI-Hib-HB) y con antineumocócica conjugada 13-valente.Se aconseja un refuerzo a los 6 años, preferentemente con DTPa (si está disponible), junto a una dosis de polio para aquellos que recibieron esquemas 2 + 1, así como vacunación con Tdpa en adolescentes y en cada embarazo, preferentemente entre las 27 y 32 semanas.La vacuna del rotavirus debería ser sistemática para todos los lactantes.Se insiste en la incorporación en el calendario de la vacuna antimeningocócica B, con esquema 2 + 1 en lactantes.Además de la inclusión de la vacuna antimeningocócica conjugada tetravalente (MenACWY) a los 12 años con rescate hasta 18 años, inclusive, el CAV-AEP recomienda que esta vacuna sea introducida también a los 12 meses de edad, sustituyendo a MenC. Igualmente, se recomienda en los mayores de 6 semanas de edad con factores de riesgo o que viajen a países de elevada incidencia de estos serogrupos.Se emplearán esquemas de dos dosis para triple vírica (12 meses y 3-4 años) y varicela (15 meses y 3-4 años). La segunda dosis se podría aplicar como vacuna tetravírica.Se recomienda la vacunación sistemática universal frente al VPH, con independencia del género, preferentemente a los 12 años, insistiendo en un mayor esfuerzo para mejorar las coberturas. La de 9 genotipos amplía la cobertura para ambos sexos.

There are only a limited number of studies on the impact of influenza in the Spanish child population. The present work intends to increase this knowledge by studying some key aspects, such as the incidence of hospital admissions, clinic variables, comorbidities, and the vaccination status in the hospitalised children.A retrospective, observational study was conducted by reviewing the medical records of children under 15 years and hospitalised due to community acquired influenza confirmed microbiologically, during 2́flu seasons (2014-2015 and 2015-2016). The study was carried out in 10 hospitals of 6cities, which represent approximately 12% of the Spanish child population.A total of 907 children were admitted to hospital with main diagnosis of influenza infection (4472 years), estimating an average annual rate of hospitalisation incidence of 0.51 cases / 1,000 children (95% CI; 0.48-0.55). Just under half (45%) of the cases had an underlying disease considered a risk factor for severe influenza, and most (74%) had not been vaccinated. The percentage of children with underlying diseases increased with age, from 26% in children6 months to 74% in children10 years. Admission to the PICU was required in 10% (92) of the cases, mainly due to acute respiratory failure.Influenza continues to be an important cause of hospitalisation in the Spanish child population. Children6 months of age and children with underlying diseases make up the majority (50%) of the cases. Many of the severe forms of childhood influenza that occur today could be avoided if current vaccination guidelines were met.

Introduction: This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age. Patients and methods: Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture. Results: A total of 501 children were recruited, of whom 91 were hospitalized. Influenza diagnosis was confirmed in 131 children (26.1%); 120 of 410 (29.3%) treated as outpatients and 11 of 91 (12.1%) hospitalized children. A total of 370 of 501 children (73.9%) had no laboratory test positive for influenza. The proportion of subjects with other respiratory viruses was 145/501 (28.9%) cases and co-infection with the influenza virus plus another respiratory virus was detected in 7/501 (1.4%) cases. Influenza virus types were: A (H1N1 and H3N2) 53.2% (67/126); B (Victoria and Yamagata) 46.0% (58/126); A + B 0.8% (1/126). The median direct medical costs associated with each case of laboratory-confirmed influenza was €177.00 (N = 131). No significant differences were observed between the medical costs associated with influenza A and B. Conclusion: Almost half of the cases were influenza virus B type. The administration of a vaccine containing influenza A and B types to children below 15 years of age might reduce the overall burden of the illness. Resumen: Introducción: El estudio se llevó a cabo para estimar la carga de enfermedad de la gripe confirmada por laboratorio en niños menores de 15 años. Pacientes y métodos: Los niños que acudieron al Hospital Universitario de Basurto con síntomas de infección respiratoria aguda y/o fiebre aislada entre noviembre de 2010 y mayo de 2011 fueron incluidos en el estudio (NCT01592799). Se tomaron 2 muestras de secreción nasofaríngea: una para un test de diagnóstico rápido en el Servicio de Urgencias y otra para análisis en laboratorio con reacción en cadena de la polimerasa en tiempo real y cultivo viral. Resultados: Se seleccionó a un total de 501 niños, de los que 91 fueron hospitalizados. El diagnóstico de gripe se confirmó en 131 (26,1%); 120/410 (29,3%) fueron tratados ambulatoriamente y 11/91 (12,1%), hospitalizados. En 370/501 niños (73,9%) el resultado no fue positivo. La proporción de otros virus respiratorios fue 145/501 (28,9%) casos y de coinfección con otro virus respiratorio además de gripe de 7/501 (1,4%). Los tipos de virus de gripe fueron: A (H1N1 y H3N2) 53,2% (67/126); B (Victoria y Yamagata) 46,0% (58/126); A + B 0,8% (1/126). El coste médico directo medio asociado con cada caso de gripe confirmada fue de 177,00 € (N = 131). No se observaron diferencias estadísticamente significativas entre el coste asociado con gripe A o B. Conclusión: Casi la mitad de los casos fueron virus de gripe B. La administración de una vacuna que incluya tipos A y B de gripe debería reducir la carga de la enfermedad.

Background Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). Case Presentation We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G>A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A>G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G>A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A>G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. Conclusions We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.