Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus (RSV) Vaccine in Healthy RSV-Seropositive Children 12-23 Months of Age.

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.

Respiratory syncytial virus (RSV) is among the main causes of bronchiolitis and pneumonia regularly leading to hospitalization in children. A safe and effective vaccine to prevent RSV infection in this age group has not yet been found, despite great efforts over several decades. This study tested a new candidate RSV vaccine, expressing 3 important pieces of the virus, in toddlers who already had a previous RSV infection. The vaccine was generally well tolerated. Vaccination triggered antibodies against RSV that were able to block the virus in laboratory tests and that persisted for 1 year.

Kernicterus in a boy with ornithine transcarbamylase deficiency: A case report.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle defect associated with severe and usually fatal hyperammonemia. This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11.55 mg/dL). The patient was a full-term male with a family history of two previous male siblings who died as newborns after acute neurologic deterioration. The patient's symptoms began at 24 h of life with lethargy that rapidly progressed to coma upon admission to the neonatal intensive care unit. Although hyperammonemia and hyperbilirubinemia were documented, hemofiltration could not be performed. OTCD diagnosis was biochemically established. Despite nutritional intervention and treatment for hyperammonemia, the patient died on the sixth day of life. At autopsy, external brain examination revealed a marked yellow pigmentation typical of kernicterus that included gray matter, particularly the thalamus and basal ganglia; dentate nuclei of the cerebellum and brain stem gray matter were also affected. Microscopic findings were consistent with the classical description of tissue damage in OTCD, including the presence of Alzheimer type II astrocytes in basal ganglia, necrosis, neuronal loss with spongiform degeneration and macrophage infiltration surrounded by astroglia. This condition may be an important comorbidity in newborns with hyperammonemia.

Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial.

BACKGROUND.: Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. METHODS.: We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6-35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424). RESULTS.: Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6-17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64-2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82-2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59-2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79-2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events. CONCLUSIONS.: Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults.

Immunogenicity and safety of inactivated quadrivalent and trivalent influenza vaccines in children 18-47 months of age.

BACKGROUND: Because inactivated trivalent influenza vaccines (TIVs) contain 1 influenza B strain, whereas 2 lineages may co-circulate, B lineage mismatch is frequent. We assessed an inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in young children. METHODS: Children aged 18-47 months who had received 2 doses of TIV in a study during the previous season (primed cohort, n = 192) were randomized 1:1 to receive 1 dose of TIV or QIV, and a further 407 children (unprimed cohort) were randomized 1:1 to receive 2 doses of TIV or QIV 28 days apart. Immunogenicity was assessed by hemagglutination-inhibition (HI) prevaccination and 28 days after each vaccination. Immunogenic non-inferiority QIV versus TIV for shared strains, and superiority against the alternate-lineage B strain were based on HI geometric mean titers (pooled analyses of primed and half of unprimed cohort with Day 56 immunogenicity assessment). Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively (NCT00985790). RESULTS: Non-inferiority for shared strains and superiority for the alternate-lineage B strain unique to QIV was demonstrated for QIV versus TIV. QIV was immunogenic against all 4 vaccine strains and 87.0%, 88.6%, 69.8% and 97.9% of children had postvaccination titers of ≥ 1:40 against A/H1N1, A/H3N2, B/Victoria and B/Yamagata, respectively. Reactogenicity and safety of QIV was consistent with TIV. CONCLUSIONS: QIV provided superior immunogenicity for the alternate-lineage B strain compared with TIV without interfering with immune responses to shared strains. Further studies are warranted to assess QIVs in children and to establish the clinical benefits of QIV versus TIV.

Recién nacidos con poliglobulia. Tratamiento comparativo con plasma y con solución salina / Polycythemia in the newborns. Comparative treatment with plasma and saline isotonic solution

Se realizó un estudio experimental, aleatorio y controlado en 32 recién nacidos con poliglobulia; se analizó comparativamente su manejo con plasma o solución salina isotonica en 16 niños de cada grupo respectivamente. No hubo diferencias estadísticamente significativas entre los dos grupos en sexo, edad gestacional y cronológica, peso corporal, estado nutricional y condiciones clínicas; tampoco en los valores plasmáticos de sodio, cloro, bicarbonato, glucosa ni complicaciones. Se concluye que el uso de solución salina es tan eficaz como el plasma para disminuir de manera significativa el hematócrito; no hay diferencias estadísticamente significativas entre ambos procedimientos. Es preferible la solución salina pues no tiene los riesgos inmunológicos ni infecciosos del plasma; es más accesible y menos costosa

Traslado del recién nacido de alto riesgo / Transportation of high risk newborn infant

Breve análisis sobre la justificación y los recursos que se requieren para el funcionamiento de un programa de transporte de recién nacidos de alto riesgo. Se presenta una opción para la organización y funcionamiento de un sistema coordinado de referencia y transporte de niños recién nacidos de alto riesgo en nuestro medio (país en vías de desarrollo)

Hemorragia intracraneana en el recién nacido: correlación clínica y ultrasonográfica / Intracraneal hemorrhage in the newborn: clinical and ultrasonographyc correlation

Se estudiaron 55 recién nacidos de riesgo elevado para desarrollar hemorragia intracraneana en el Departamento de Neonatología del Instituto Nacional de Pediatría. La frecuencia de hemorragia intracraneana fue de 41.8%. Se analizaron los antecedentes, el cuadro clínico, la exploración neurológica, y las secuelas neurológicas con un seguimiento de 2 años, y su relación con la hemorragia intracraneana. Se concluye que la hemorragia intracraneana es frecuente en el recién nacido prematuro y/o recién nacido de término con hipoxia perinatal. Este diagnóstico no implica necesariamente un mal pronóstico. El estudio de elección es el ultrasonido de tiempo real transfontanela; la hemorragia intracraneana siempre debe ser considerada como una urgencia para inicial el tratamiento oportuno y evitar secuelas a mediano y largo plazo.