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Background: Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization., Methods: This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6-14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (27 0/7 -36 6/7 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination., Results: 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5-77.1%) versus placebo (90.0-99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related., Conclusions: Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience., Clinical Trial Registration: ClinicalTrials.gov: NCT02422264., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [BAN reports grant from the GSK group of companies (GSK) and personal fees from Pfizer, MSD and Sanofi Pasteur. BC, MAC, NMes, NMey and SOK are employees of GSK, and BC and NMes own GSK restricted shares. FMT, KPP, OGV, SAH and TN’s institutions received grants from GSK during the conduct of the study. FMT’s institution received financial support from GSK during the conduct of the study, as well as financial and non-financial support outside the submitted work; he also received personal fees from Pfizer, Novavax, MSD and Sanofi Pasteur; his institution also received financial support as trial fees from Ablynx, Jansen, Regeneron, Medimmune, Pfizer, MSD, Sanofi Pasteur, Novavax and Novartis, as well as non-financial support from Pfizer and MSD and grants from MSD and AstraZeneca. JMMA reports receiving fees and non-financial support from GSK during the conduct of the study, as well as fees from GSK, Pfizer and MSD outside the submitted work. LK is working as consultant for GSK. SAH is member of ad-hoc advisory committees for GSK and Sanofi Pasteur and he has a patent for novel triple adjuvant issued. ACM, FOT, GVZ, JGS, JTRA, MB, MJCO, MMV, MV, PGM, PM and ZS declare no conflicts of interest.]., (Copyright © 2019 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Background: We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM 197 -conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent)., Methods: In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM 197 -conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 μg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed., Results: 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded., Conclusion: Addition of 19A and 6A CRM 197 -conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study evaluated the immunogenicity and reactogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus virus-Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) and a 10-valent pneumococcal conjugate vaccine (PHiD-CV) coadministered with a quadrivalent meningococcal conjugate vaccine (MenACWY-TT) in infants/toddlers., Methods: In this open, controlled, phase III study (NCT01144663), 2095 healthy infants were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age or MenACWY-TT, MenC-CRM197, or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age. Immunogenicity of DTPa-HBV-IPV/Hib was evaluated in exclusive randomized subsets of 25% of participants from each group postprimary, prebooster and postbooster vaccination, whereas immunogenicity of PHiD-CV was evaluated at all time points. Reactogenicity was evaluated on the total vaccinated cohorts during 8 days after each vaccination., Results: For each DTPa-HBV-IPV/Hib antigen, ≥97.2%, ≥76.5% and ≥97.9% of participants had seropositive/seroprotective levels 1 month postprimary vaccination, before the booster dose and 1 month postbooster, respectively. For each vaccine pneumococcal serotype, ≥74.0% of infants had antibody concentrations ≥0.35 μg/mL at 1 month postprimary vaccination, and robust increases in antibody geometric mean concentrations were observed from prebooster to postbooster. Redness was the most frequent solicited local symptom at the DTPa-HBV-IPV/Hib and PHiD-CV injection sites, reported after up to 47.7% and 57.0% of doses postprimary and postbooster vaccination, respectively., Conclusions: Primary and booster vaccinations of infants/toddlers with DTPa-HBV-IPV/Hib and PHiD-CV coadministered with MenACWY-TT were immunogenic with clinically acceptable reactogenicity profiles. These results support the coadministration of MenACWY-TT with routine childhood vaccines.

Background: This was the first study evaluating the immunogenicity and safety of the quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) coadministered with routine childhood vaccines in young infants., Methods: In this open, randomized, controlled, phase III study (NCT01144663), 2095 infants (ages 6-12 weeks) were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age, or MenACWY-TT, MenC-cross-reactive material (CRM197) or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age. Immune responses were measured by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement. Solicited and unsolicited symptoms were recorded during 8 and 31 days post-vaccination, respectively, and serious adverse events throughout the study., Results: Noninferiority of immune responses to MenC induced by 2 or 3 doses of MenACWY-TT versus 2 doses of MenC-TT or MenC-CRM197 was demonstrated. Predefined criteria for the immunogenicity of MenACWY-TT to MenA, MenW and MenY were met. One month after 2 or 3 primary MenACWY-TT doses, ≥93.1% and ≥88.5% of infants had rSBA and hSBA titers ≥1:8 for all serogroups. The robust increases in rSBA and hSBA titers observed for all vaccine serogroups postbooster vaccination suggested that MenACWY-TT induced immune memory. MenACWY-TT coadministered with childhood vaccines had a clinically acceptable safety profile., Conclusions: This study supports the coadministration of MenACWY-TT with routine childhood vaccines as 2 or 3 primary doses during infancy followed by a booster dose in the second year of life.

We present the case of a 4-day-old newborn with serious dehydration, polypnea, hypertonus and lethargy. Blood analysis showed severe metabolic acidosis with ketonemia, ketonuria and elevation of the GAP anion. Urine analysis revealed increased excretion of 2-methyl-3-hydroxybutyrate acid, tiglycine, and 2-methylacetoacetate acid. Neonatal onset of mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is exceptional. Most patients have no clinical symptoms in the neonatal period. This entity should be considered in patients with acute metabolic acidosis and ketosis with normal glycemia and aciduria. The urine contains large amounts of 2-methylacetoacetate and its decarboxylation products. In the neonatal period, this inherited disorder of metabolism can produce severe hydroelectrolyte disorders in the form of a gradual process or acute episodes, which can occasionally be fatal.

Group A beta-hemolytic streptococcus (GAS) causes almost 10% of acute hematogenous osteomyelitis (AHOM). These entities are frequently located in long bones (femur, tibia and humerus), and only 6-8% of all AHOM are located in the pelvis. This uncommon localization delays diagnosis and can lead to inappropriate management, with negative effects on outcomes. We present the case of a 6-year-old boy with high fever, pain in the right hip and difficulty in walking due to pelvic AHOM and septic shock caused by GAS. We also provide a review of the literature.

Non-Hodgkin's lymphomas are the most common cancers in children with human immunodeficiency virus (HIV) infection. Extranodal disease is the most common form of clinical presentation. Treatment with aggressive chemotherapy and highly active antiretroviral therapy has improved the prognosis of these children. We present a 10-year-old severely immunocompromised girl with HIV infection and non-Hodgkin's lymphoma manifested by a muscle mass.

Introduction: Several degenerative neurological diseases are caused by mutations in the mitochondrial gene coding for subunit 6 of the ATPase. Thus, NARP (neurogenic weakness, ataxia, and retinitis pigmentosa) and Leigh syndromes are associated to a T8993G mutation when the percentage of mutant mitochondrial DNA is low (60 90%) or high (>90%), respectively. Leigh syndrome is also caused by a second mutation in the same position T8993C., Case Report: The patient, a boy that died at 6 months, had generalized hypotonia, psychomotor delay, hepatomegaly, choreic movements and hyporreflexia. MRI showed hypodensities in the basal ganglia and brain stem as well as hyperlactacidemia. Molecular genetic analysis of the mitochondrial DNA showed that the patient had the T8993G mutation in a percentage higher than 95%. No mutated DNA was detected in blood of the proband s mother, maternal aunt and grandmother., Conclusions: The point mutation T8993G may occur de novo, at high levels, causing neurodegenerative diseases.

Objective: The aim of this study was to investigate the incidence, clinical and radiological particularities of primary pulmonary tuberculosis in children between 10 to 16 year-old in our community., Patients and Methods: The medical records and chest X-ray of all children under 16 years old diagnosed of primary pulmonary tuberculosis between 1982 to 1996, and a similar characteristics control group diagnosed of bacterial pneumonia were reviewed. The difference between teenager with tuberculosis and pneumonia and between patients with tuberculosis under 10 years and order were analysed., Results: Between January 1982 and December 1996, 83 children with age range from 10 to 16 years were diagnosed of primary pulmonary tuberculosis. The incidence has been 15,5 cases/100000 h < 16 years/year. The primary pulmonary tuberculosis whole incidence in children under 16 year-old has been 17 cases/100000 h/year (182 cases). The adolescents fits to 40.5% of the hold group. 51.2% were girls and 49.8% were boys. Middle age has been 14.2+/-0.18 years with a progressive increased with the age. Anorexia (38% vs. 16.6%) and asthenia (38% vs 19.4%) have been more frequents in teenagers with tuberculosis. Cough has been the most frequent symptom in both groups (61.9% and 77.7%), and respiratory distress has been the most characteristic of tuberculosis (17.8% vs 2.7%). Thoracic pain was more frequent in patients with tuberculosis 10 years or older (57.8% and 7.8%). Laboratory values are not specific. Pleural effusion (46.4% vs 22.2%) and mediastinal lymphadenophaty (60.1% vs. 40.4%) were the most characteristic X-ray finding in teenagers and children under 10 years with primary pulmonary tuberculosis respectively., Conclusions: Primary pulmonary tuberculosis has a high incidence in the teenager population in our community with a progressive increased with the age. The clinical and laboratory values are unspecific in this age group. The most characteristic X-ray finding is pleural effusion (46.4% of the patients).

Objective: The aim of this study was to determine the incidence, clinical features and outcome of nontraumatic hemorrhagic stroke in children., Patients and Methods: We performed a retrospective study of children with nontraumatic hemorrhagic stroke (codes 430-432 of the International Classification of Disease, 9th revision)., Results: Between January 1982 and December 1995, twenty-one children less than 16 years of age with nontraumatic hemorrhagic stroke were admitted to our hospital. The incidence rate for hemorrhagic stroke was 2.3 cases per 100,000 per year which constituted 67.7% of all strokes in children. There was a slight predominance of males (1.62:1). Onset of symptoms was sudden in 61.9% of cases and gradual in 38%. The most commo symptoms were altered consciousness (71.4%) and hemiparesis (61.9%). Vascular malformations constituted the largest etiological group (42.8%) followed by the hemorrhages into cerebral tumors (9.5%). In 28.5% of the cases no cause could be found. Surgery was carried out in 38% of the cases. There was an overall mortality of 19% and a post-operative mortality of 25%., Conclusions: Hemorrhagic stroke is a rare event in childhood. Prompt surgical management decreases the mortality rate and improves the outcome of these patients.

We have studied 2,224 children and adolescents of both sexes, ranging between 2 and 18 years of age, at five schools in the city of Madrid. We determined the lipid profile: total cholesterol (T-C), cholesterol bound to high density lipoproteins (HDL-C), cholesterol bound to low density lipoproteins (LDL-C), cholesterol bound to very low density lipoproteins (VLDL-C), triglycerides (TG), apolipoprotein AI and apolipoprotein B100 (Apo A1 and Apo B100, respectively). In relationship to age and sex, in males, as age increases, there is an elevation in LDL-C and TG and a diminution in T-C, HDL-C, Apo AI and Apo B100. There are no changes in VLDL-C. In females, there is a diminution in LDL-C, TG, Apo-B100 and an increase in HDL-C, Apo AI and T-C, with the increase in T-C being found only in those older than 15 years.

A case of an invasive pulmonary aspergillosis with pneumopericardium and pneumothorax in an immunocompromised child of 5 years is reported. He was treated with thoracic drainage, amphotericin B and itraconazole. The course was satisfactory.

Metastatic cord compression is a rare complication of malignant diseases in childhood. The most common causes are bone and soft tissue sarcomas, neuroblastoma, lymphoma and leukemia. The clinical manifestations, diagnosis, treatment and evolution of eight children with metastatic cord compression are presented. Diagnosis was based on computerized tomography that was pathological in all the cases, and confirmed by myelography in four patients. The cytological analysis of the cerebrospinal fluid was made in three patients being negative for tumoral cells in all of them. Treatment consisted on radiotherapy, chemotherapy and/or surgery depending on the tumor histology. Decompressive laminectomy was made in patients who did not show previous evidence of cancer. Functional prognosis was related with the degree of disablement at diagnosis and treatment.