Immunisation schedule of the Spanish Association of Pediatrics: 2024 recommendations.

The AEP Immunization Calendar for 2024, with its immunization recommendations for pregnant women, children and adolescents residing in Spain, marks the 25th edition since the first one was introduced in 1995, being annual since 2003, as a vaccination calendar, and since 2023 as immunization schedule due to the inclusion of a monoclonal antibody for the prevention of RSV disease. Novelties for this year include the following: The rest of the recommendations from the previous calendar remain unchanged.

Immunisation schedule of the Spanish Association of Paediatrics: 2023 Recommendations.

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.

Societal Preferences for Meningococcal B Vaccination in Children: A Discrete Choice Experiment in Spain.

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.

Clinical characteristics, health care resource utilization and direct medical costs of Rotavirus hospitalizations in Spain (2013-2018).

Rotavirus (RV) is the most common cause of severe gastroenteritis (GE) in infants and young children worldwide and is associated with a significant clinical and economic burden. The objective of this study was to analyze the characteristics, healthcare resource utilization and the direct medical costs related to RVGE hospitalizations in Spain. An observational, multicenter, cross-sectional study was conducted from June 2013 to May 2018 at the pediatric departments of 12 hospitals from different Spanish regions. Children under 5 years of age admitted to the hospital with a confirmed diagnosis of RVGE were selected. Data on clinical characteristics, healthcare resource use and costs were collected from patient records and hospital databases. Most children hospitalized for RVGE did not have any previous medical condition or chronic disease. Forty-seven percent had previously visited the Emergency Room (ER), 27% had visited a primary care pediatrician, and 15% had received pharmacological treatment prior to hospital admission due to an RVGE episode. The average length of a hospital stay for RVGE was 5.6 days, and the mean medical costs of RVGE hospitalizations per episode ranged from 3,940€ to 4,100€. The highest direct medical cost was due to the hospital stay. This study showed a high burden of health resource utilization and costs related to the management of cases of RVGE requiring hospitalization. RV vaccination with high coverage rates should be considered to minimize the clinical and economic impacts of this disease on the health-care system.

Immunization schedule of the Pediatric Spanish Association: 2022 recommendations.

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.

Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.

Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune lymphoproliferative syndrome (ALPS) is a PIRD due to an apoptotic defect in Fas-FasL pathway and characterized by benign and chronic lymphoproliferation, autoimmunity and increased risk of lymphoma. Clinical manifestations and typical laboratory biomarkers of ALPS have also been found in patients with a gene defect out of the Fas-FasL pathway (ALPS-like disorders). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), we identified more than 600 patients suffering from 24 distinct genetic defects described in the literature with an autoimmune lymphoproliferative phenotype (ALPS-like syndromes) corresponding to phenocopies of primary immunodeficiency (PID) (NRAS, KRAS), susceptibility to EBV (MAGT1, PRKCD, XIAP, SH2D1A, RASGRP1, TNFRSF9), antibody deficiency (PIK3CD gain of function (GOF), PIK3R1 loss of function (LOF), CARD11 GOF), regulatory T-cells defects (CTLA4, LRBA, STAT3 GOF, IL2RA, IL2RB, DEF6), combined immunodeficiencies (ITK, STK4), defects in intrinsic and innate immunity and predisposition to infection (STAT1 GOF, IL12RB1) and autoimmunity/autoinflammation (ADA2, TNFAIP3,TPP2, TET2). CTLA4 and LRBA patients correspond around to 50% of total ALPS-like cases. However, only 100% of CTLA4, PRKCD, TET2 and NRAS/KRAS reported patients had an ALPS-like presentation, while the autoimmunity and lymphoproliferation combination resulted rare in other genetic defects. Recurrent infections, skin lesions, enteropathy and malignancy are the most common clinical manifestations. Some approaches available for the immunological study and identification of ALPS-like patients through flow cytometry and ALPS biomarkers are provided in this work. Protein expression assays for NKG2D, XIAP, SAP, CTLA4 and LRBA deficiencies and functional studies of AKT, STAT1 and STAT3 phosphorylation, are showed as useful tests. Patients suspected to suffer from one of these disorders require rapid and correct diagnosis allowing initiation of tailored specific therapeutic strategies and monitoring thereby improving the prognosis and their quality of life.

[Immunisation schedule of the Pediatric Spanish Association: 2021 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2021.

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.

Prevalence and Clinical Manifestations of Congenital Cytomegalovirus Infection in a Screening Program in Madrid (PICCSA Study).

BACKGROUND: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Up to 15%-20% of infected newborns will develop long-term sequelae such as hearing loss and neurologic abnormalities. The aim of this study was to investigate the prevalence of congenital CMV infection (cCMV) and associated clinical abnormalities in Spain. METHODS: A prospective screening for cCMV by viral load in saliva was performed. Saliva samples were obtained within the first 72 hours of life in a maternity ward in Madrid (Spain), during a 1-year period. All positive screening tests were confirmed with viral load in urine. Clinical, laboratory, auditory, visual and cerebral imaging assessments were performed in all children with cCMV. RESULTS: Of the 4097 neonates born during the study period, 3190 (78%) were included. CMV viral load in saliva was detectable in 24/3190 (0.75%) children, and congenital infection was confirmed in 15/3190 (0.47%, CI 95%: 0.29%-0.77%). Positive predictive value was 62.5% (CI 95%: 46.5%-76.1%). Two infants presented symptoms at birth. Eight (53.3%) children showed abnormalities in magnetic resonance imaging; most of them isolated white matter abnormalities. Newborns with abnormalities in magnetic resonance imaging showed higher viral loads in blood and saliva (P = 0.04). CONCLUSIONS: One in 200 neonates born in our hospital presented a cCMV infection. CMV viral load in saliva has been shown to be a simple and highly accepted screening method but should be confirmed by CMV detection in urine. In spite of the fact that half of infected children had abnormalities in cerebral imaging, diagnosis during the neonatal period would have been impossible without a screening program in most cases.

[Immunisation schedule of the Spanish Association of Paediatrics: 2020 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2020.

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.

Impact of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children under 15 years old in Madrid, Spain, 2007 to 2016: The HERACLES clinical surveillance study.

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Using the data from the HERACLES clinical surveillance study (2007-2016), we describe the population impact of the 13-valent pneumococcal conjugate vaccine (PVC13) on invasive pneumococcal disease (IPD) in children <15 years of age in the Community of Madrid, Spain. After six years of the inclusion of PCV13 in the vaccination calendar (2010-2016), and despite changes in the Regional Immunization Programme that limited its availability, the net benefit incidence rate (IR) of IPD fell by 70.1% (IRR 0.3 [95% CI: 0.22-0.4]; p ≤ 0.001), mainly due to a significant reduction (91%) in the PCV13 serotypes (IRR 0.09 [95% CI: 0.05-0.16], p ≤ 0.001). Furthermore, no significant changes were detected in the IR of IPD caused by non-PCV13 serotypes. The IRs of the aggressive, resistant and most prevalent serotype in the analysed population, the 19A serotype, dramatically decreased from the beginning to the end of the study (98%) [IRR 0.03 (95% CI: 0.00-0.19), p ≤ 0.001], to its almost total disappearance. Remarkably, this reduction led to a pronounced decline in the percentage of cefotaxime-resistant isolates and the incidence of meningitis cases. Assessment of the clinical impact revealed a reduction in the number of all clinical presentations of IPD, confirming the effectiveness of the PCV13. Finally, PCV13 detected by PCR is predicted to have a stronger impact than the one based on culture methods, which can overlook more than 20% of cases of IPD, mainly pleural empyemas.

[Immunisation schedule of the Spanish Association of Paediatrics: 2019 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2019.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics annually publishes the immunisation schedule considered optimal for children resident in Spain, according to available evidence on current vaccines. As regards funded immunisations, the 2+1 strategy (2, 4, 11 months) with hexavalent (DTPa-IPV-Hib-HB) and 13-valent pneumococcal vaccines are recommended. Administration of the 6-year booster dose with DTPa is recommended, with a poliomyelitis dose for children who had received the 2+1 scheme, as well as Tdap vaccine for adolescents and pregnant women in every pregnancy between 27 and 32 weeks gestation. The 2-dose scheme should be used for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years). MMRV vaccine could be applied as the second dose. Vaccination against HPV is recommended in both genders, preferably at 12 years of age. A stronger effort should be made to improve vaccination coverage. The new 9-valent vaccine is now available, expanding the coverage for both genders. Tetravalent meningococcal vaccine (MenACWY) is recommended at 12 months and 12-14 years, with a catch-up up at 19 years of age. It is also recommended in infants older than 6 weeks of age with risk factors, or travellers to countries with high incidence of ACWY meningococcal serogroups. As regards non-funded immunisations, it is recommended meningococcal B vaccination, with a 2+1 schedule, and requests that it be included in the National Immunisation Program. Vaccination against rotavirus is recommended in all infants.

[Child hospital admissions associated with influenza virus infection in 6 Spanish cities (2014-2016)]. / Hospitalizaciones infantiles asociadas a infección por virus de la gripe en 6 ciudades de España (2014-2016).

INTRODUCTION: 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. METHODS: 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. RESULTS: A total of 907 children were admitted to hospital with main diagnosis of influenza infection (447 <2 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 children <6 months to 74% in children >10 years. Admission to the PICU was required in 10% (92) of the cases, mainly due to acute respiratory failure. CONCLUSION: Influenza continues to be an important cause of hospitalisation in the Spanish child population. Children <6 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.

[Immunisation schedule of the Spanish Association of Paediatrics: 2018 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría (CAV-AEP): recomendaciones 2018.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics annually publishes the immunisation schedule considered optimal for children resident in Spain, according to available evidence on current vaccines. Regarding funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTPa-IPV-Hib-HB) and 13-valent pneumococcal vaccines are recommended. Administration of the 6-year booster dose with DTPa is recommended, and a poliomyelitis dose for children who had received the 2+1 scheme, as well as Tdap vaccine for adolescents and pregnant women in every pregnancy between 27 and 32 weeks' gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). MMRV vaccine could be applied as the second dose if available. Coverage of human papillomavirus vaccination in girls aged 12 with a two dose scheme (0, 6 months) should be improved. Information and recommendation for male adolescents about potential beneficial effects of this immunisation should be provided as well. The new 9 genotypes vaccine is now available, expanding the coverage for both gender. Regarding non-funded immunisations, Committee on Vaccines of the Spanish Association of Paediatrics recommends meningococcal B vaccination, with a 3+1 schedule, and requests to be included in the National Immunisation Program. Tetravalent meningococcal vaccine (MenACWY) is recommended to adolescents (14-18 years) who are going to live in countries with systematic vaccination against ACWY serogroups, and people >6 weeks of age with risk factors or travellers to countries with very high incidence. Vaccination against rotavirus is recommended in all infants.

Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients.

GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK)-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype. Patients with more severe clinical complications demonstrated a senescent T-cell phenotype whereas patients with lower clinical score had undetectable changes relative to controls. In contrast, patients' NK-cells demonstrated an immature/activated phenotype that did not correlate with clinical score, suggesting an intrinsic NK-cell defect. These studies will help us to determine the contribution of T- and NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help to establish the most accurate therapeutic options for these patients. Asymptomatic patients may be taken into consideration for hematopoietic stem cell transplantation when dysregulation of T-cell and NK-cell compartment is present.