D. Moreno-Pérez

Calendario de vacunaciones de la Asociacion Espanola de Pediatria: recomendaciones 2010

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the prevention of this disease. In anticipation of upcoming national and international studies, the Committee recommends the vaccine for the control of disease outbreaks, and insists on the need to be available in pharmacies. Finally, it emphasises the need to bring incomplete vaccinations up to date following the catch-up immunisation schedule.

Potent and sustained antiviral response of raltegravir-based highly active antiretroviral therapy in HIV type 1-infected children and adolescents.

Background: There are pediatric patients receiving many highly active antiretroviral therapy (HAART) regimens entailing drug resistance mutations that complicate HAART effective therapies. Methods: This was a multicenter retrospective study of 19 multidrug-resistant children and adolescents enrolled from July 2007 to October 2009. Patients were nonresponders because no reduction in HIV type 1 (HIV-1) RNA to undetectable levels was observed during their previous antiretroviral treatment history. The long-term effectiveness of raltegravir (RAL)-based salvage therapy was assessed through a longitudinal analysis of immunologic, virologic, and clinical status of the patients. Results: Median age was 16.0 (15.0–18.0) years. At baseline, median HIV-1 RNA was 10,000 (4.0 log10 copies/mL) (interquartile range [IQR]: 4300–83,000), and median CD4+T-cell count was 329 (18.2% cells/&mgr;L) (IQR: 175–452). The backbone regimen included at least 1 fully active drug in 17/19 (89%) patients. Median follow-up with HAART including RAL was 80.1 weeks (IQR: 49.4–96.4): 16/19 (84%) exposed for >120 weeks and 6/19 (32%) >100 weeks. After RAL-based therapy, 4/19 (21%) patients achieved HIV-1 RNA <400 copies and 13/17 (68%) reached HIV-1 RNA <50 copies: 6 (32%) within the first month and 7 (37%) within the first 4 months. CD4+T-cell recovery (70% to 90% of the baseline values) was observed in 17/19 (89%) patients. No deaths, AIDS-defining illnesses, or symptoms of severe intolerance were recorded. Only 2 patients experienced mild-moderate short-term skin rash. Two (11%) patients had sustained and optimum adherence to HAART. No patients showed resistance mutations to RAL after follow-up. Conclusions: We observed a sustained antiviral response and improved immunologic indices in multidrug-resistant pediatric patients, most of whom had received RAL as part of salvage regimens with at least 1 fully active drugs.

Documento de consenso de la Sociedad Española de Infectología Pediátrica sobre la tuberculosis resistente a fármacos

Drug resistant tuberculosis (TB-R), and in particular, multidrug resistant tuberculosis (MDR-TB) is a global public health problem, as well as a problem in our country. Cases of TB-R and MDR-TB have increased mainly in HIV, immigrant and socially disadvantaged populations, but a notable increase in the general population has also been observed. This aspect reinforces the need for a systematic study of sensitivity of all the isolates in a reference laboratory to optimally guide the treatment. Children are especially vulnerable to this severe disease due to the limited knowledge of second line anti-tuberculous drugs, in terms of their pharmacokinetic data, optimal doses, or their long term toxicity, all this eventually resulting in the compassionate use of drugs. Another aspect which further complicates the management of R-TB in children is the limited yield of cultures, which frequently leads to clinician designing drug combinations according to the sensitivity of the initial strain. The epidemiological pattern in our country has currently changed. There is a reported increase in isoniazid-resistant strains; therefore, a four drugs regime is mandatory for the initial period in children, until reliable sensitivity results are available. Treatment should be directly observed or at least supervised by paediatricians. The management of latent infections or exposure to a resistant TB case also requires an accurate, strict and prolonged supervision by expert paediatricians. Authorities and health care professionals who deal with TB should be prepared to face this new phenomenon with appropriate measures. The knowledge of second line drugs for children, as well as mechanisms to ensure the therapeutic adherence and long term control of disease, are essential.

Immunization schedule of the Spanish Association of Pediatrics: 2012 recommendations

The Advisory Committee on Vaccines of the Spanish Association of Pediatrics (CAV-AEP) updates the immunization schedule every year, taking into account epidemiological data as well as evidence on the effectiveness and efficiency of vaccines. The present schedule includes grades of recommendation. We have graded as routine vaccinations those that the CAV-AEP believes all children should receive; as recommended those that fit the profile for universal childhood immunization and would ideally be given to all children, but that can be prioritized according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in situations of risk. Immunization schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Nevertheless, the achievement of a unified immunization schedule in all regions of Spain is a top priority for the CAV-AEP. Based on the latest epidemiological trends, the main changes introduced to the schedule are the administration of the first dose of the MMR and the varicella vaccines at age 12 months (12-15 months) and the second dose at age 2-3 years, as well as the administration of the Tdap vaccine at age 4-6 years, always followed by another dose at 11-14 years of age. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-14 years must increase. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunization schedule. Universal vaccination against varicella in the second year of life is an effective strategy and therefore a desirable objective. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Finally, it emphasizes the need to bring incomplete vaccinations up to date following the catch-up immunization schedule.

Vacunación antigripal universal en pediatría, ¿sí o no?

INTRODUCTIONnThe recommendations on influenza vaccination are not homogeneous between countries, with striking differences between the current recommendations in United States and Europe.nnnOBJECTIVEnThe objective of the study is to determine the efficacy, effectiveness and safety of the current flu vaccine (trivalent inactivated vaccine and adapted to the cold [LAIV] live virus vaccine) in healthy children, and to try and answer the following question: universal immunization against influenza in Paediatrics, yes or no?nnnMATERIAL AND METHODSnA scheme of work based on the five standard steps of evidence or science-based medicine was used: 1) question, 2) search, 3) valuation, 4) applicability and 5) adequacy.nnnRESULTSnNine systematic reviews, published between 2005 and 2012, were selected that answered our clinical question, and which included the best available information (randomised clinical trials, cohort studies and case studies).nnnCONCLUSIONSnThe flu vaccine in childhood has the right cost - benefit - risk relationship. In all systematic reviews the efficacy of the flu vaccine varied between 58%-65%, and effectiveness between 28%-61%. Both efficacy and effectiveness increase with age, and there are limited studies showing sufficient evidence in children < 2 years. There are further areas to develop: more and better clinical trials on influenza vaccines in infants from 6 to 23 months; further research to achieve better influenza vaccines (addition of adjuvants, higher doses in children between 6 and 23 months, and study the LAIV vaccine in children between 6 and 23 months); and improvement in the prediction of vaccine strains responsible for the outbreak.

Combined haemophilus Influenzae Type B- neisseria Meningitidis Serogroup C Vaccine Is Immunogenic and Well Tolerated in Preterm Infants When Coadministered With Other Routinely Recommended Vaccines

Background: Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. Methods: In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks gestation; n = 107, 31–36 weeks gestation) and 150 full-term infants (>36 weeks gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4–6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. Results: There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. Conclusions: Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.

Vacunación frente al meningococo B. Posicionamiento del Comité Asesor de Vacunas de la Asociación Española de Pediatría

Meningococcal invasive disease, including the main clinical presentation forms (sepsis and meningitis), is a severe and potentially lethal infection caused by different serogroups of Neisseria meningitidis. Meningococcal serogroup B is the most prevalent in Europe. Most cases occur in children, with a mortality rate of 10% and a risk of permanent sequelae of 20-30% among survivors. The highest incidence and case fatality rates are observed in healthy children under 2-3 years old, followed by adolescents, although it can occur at any age. With the arrival in Spain of the only available vaccine against meningococcus B, the Advisory Committee on Vaccines of the Spanish Association of Paediatrics has analysed its preventive potential in detail, as well as its peculiar administrative situation in Spain. The purpose of this document is to publish the statement of the Committee as regards this vaccination and the access to it by the Spanish population, taking into account that it has been only authorized for people at risk. The vaccine is available free in the rest of Europe for those who want to acquire it, and in some countries and regions it has been introduced into the systematic immunisation schedules. The Committee considers that Bexsero® has a profile of a vaccine to be included in the official schedules of all the Spanish autonomous communities and insists on the need for it to be available in pharmacies for its administration in all children older than 2 months.

Decreased activation-induced cell death by EBV-transformed B-cells from a patient with autoimmune lymphoproliferative syndrome caused by a novel FASLG mutation

Background:Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency characterized by chronic lymphoproliferation, autoimmune manifestations, expansion of double-negative T-cells, and susceptibility to malignancies. Most cases of ALPS are caused by germline or somatic FAS mutations. We report the case of an ALPS patient due to a novel homozygous Fasligand gene mutation (ALPS-FASLG).Methods:ALPS biomarkers were measured and FASLG mutation was identified. Functional characterization was carried out based on activation-induced cell death (AICD) and cytotoxicity assays.Results:This report describes the cases of a patient who presented a severe form of ALPS-FASLG, and his brother who had died due to complications related to ALPS. Moreover, in another family, we present the first case of lymphoma in a patient with ALPS-FASLG. Functional studies showed defective Fasligand-mediated apoptosis, cytotoxicity, and AICD in T-cell blasts. Otherwise, expression of the FASLG gene and corresponding protein was normal, but the shedding of the Fasligand was impaired in T-cells. Additionally, analyzing Epstein-Barr virus (EBV)-transformed B-cells, our results indicate impaired AICD in ALPS-FASLG patients.Conclusion:Patients with autosomal recessive inheritance of ALPS-FASLG have a severe phenotype and a partial defect in AICD in T- and B-cell lines. The Fasligand could play a key role in immune surveillance preventing malignancy.

Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice

Maraviroc (MVC) is not approved for HIV-1-infected paediatric patients. This is the first assessment of the use of MVC-based salvage therapy in vertically HIV-1-infected paediatric patients in clinical settings. The results suggest that MVC-based salvage therapy is useful in children and adolescents with extensive resistance profile leading to maintained virological suppression in up to 88% of the patients with CCR5-tropic virus. The likelihood of treatment success might increase when MVC is combined with other active drugs.

Vacunación frente a la gripe estacional en la infancia y la adolescencia. Recomendaciones del CAV-AEP para la campaña 2011-2012

Seasonal influenza vaccination in children and adolescents. Recommendations of the CAV-AEP for the campaign Abstract The Advisory Committee on Vaccines of the Spanish Association of Paediatrics esta- blishes annual recommendations on influenza vaccination in childhood before the onset of influenza season. Routine influenza vaccination is particularly beneficial when the strategy is aimed at children older than 6 months of age with high-risk conditions and their home con- tacts. The recommendation of influenza vaccination in health workers with children is also emphasised.