Molecular epidemiology of pneumococcal carriage in children from Seville, following implementation of the PCV13 immunization program in Andalusia, Spain.

INTRODUCTION: The 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination programme was introduced in December 2016 in Andalusia. METHODS: A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period), were used for comparison of serotype/genotype distributions and antibiotic resistance rates. RESULTS: Overall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11% vs 38%, p = 0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (p = 0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. CONCLUSIONS: There was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.

Endocarditis infecciosa en pacientes pediátricos de Andalucía (España), 2008-2020 / Infective endocarditis in paediatric patients from Andalusia (Spain), 2008-2020

Introducción: La endocarditis infecciosa (EI) pediátrica es un cuadro grave con mortalidad significativa. La información en España es limitada y procede de series de casos de centros únicos. El objetivo fue describir la epidemiología, la clínica, la microbiología y los resultados de la EI pediátrica en Andalucía. Pacientes y métodos: Estudio descriptivo observacional retrospectivo multicéntrico de pacientes <18años con diagnóstico de EI en 6 hospitales andaluces durante el periodo 2008-2020. Resultados: Se identificaron 44 episodios de EI (41 pacientes) con mediana de edad de 103 meses (RIQ 37-150 meses). Las cardiopatías congénitas (CC) fueron el principal factor predisponente, presente en 34 casos (77%). Un total de 21 (48%) episodios de EI ocurrieron en pacientes con material protésico. Estos tuvieron una mayor tasa de CC (p=0,002) y disfunción orgánica (p=0,04) que aquellos con válvula nativa. La fiebre fue un síntoma prácticamente universal asociada con insuficiencia cardíaca en el 23% de los episodios. Staphylococcus aureus (25%), estafilococos coagulasa negativos (18%) y Streptococcus viridans (14%) fueron los microorganismos aislados con mayor frecuencia y tres (7%) pacientes portadores de catéter venoso central tuvieron una infección fúngica. Se observaron complicaciones tromboembólicas en el 30% de los episodios, y tuvieron requerimientos quirúrgicos el 48% de casos. La mortalidad fue del 9%. El material protésico y la PCR >140mg/l fueron predictores independientes de EI complicada. Conclusiones: Los hallazgos del estudio subrayan la elevada morbilidad de la EI pediátrica. La información generada podría favorecer la identificación de los perfiles epidemiológicos y clínicos de los niños con EI y formas complicadas.(AU)

Introduction: Paediatric infective endocarditis (IE) is a serious condition associated with significant mortality. Information in Spain is limited and comes from case series from single centres. The aim was to describe the epidemiology, clinical features, microbiology and outcome of paediatric IE in Andalusia. Patients and methods: Multi-centre descriptive observational retrospective study of patients <18years old with a diagnosis of IE who were admitted to six Andalusian hospitals during 2008-2020. Results: 44 episodes of IE (41 patients) with a median age of 103months (IQR 37-150 months) were identified. Congenital heart disease (CHD) was the main predisposing factor, identified in 34 cases (77%). A total of 21 (48%) episodes of IE occurred in patients with prosthetic material. These had higher rate of CHD (P=.002) and increased end organ dysfunction (P=.04) compared to those with native valve. Fever was an almost universal symptom, associated in 23% of the episodes with heart failure. Staphylococcus aureus (25%) followed by coagulase-negative staphylococci (18%) and Streptococcus viridans (14%) were the most frequently isolated microorganisms, and three (7%) patients with central venous catheters had a fungal infection. Thromboembolic events were observed in 30% of the episodes, surgical intervention was required in 48% of cases. Mortality rate was 9%. Prosthetic material and CRP >140mg/L were independent predictors of complicated IE. Conclusions: Our findings emphasise the high morbidity of paediatric IE. The information provided could be useful for the identification of epidemiological and clinical profiles of children with IE and complicated forms.(AU)

Infective endocarditis in paediatric patients from Andalusia (Spain), 2008-2020.

INTRODUCTION: Paediatric infective endocarditis (IE) is a serious condition associated with significant mortality. Information in Spain is limited and comes from case series from single centres. The aim was to describe the epidemiology, clinical features, microbiology and outcome of paediatric IE in Andalusia. PATIENTS AND METHODS: Multi-centre descriptive observational retrospective study of patients <18 years old with a diagnosis of IE who were admitted to six Andalusian hospitals during 2008-2020. RESULTS: 44 episodes of IE (41 patients) with a median age of 103 months (IQR 37-150 months) were identified. Congenital heart disease (CHD) was the main predisposing factor, identified in 34 cases (77%). A total of 21 (48%) episodes of IE occurred in patients with prosthetic material. These had higher rate of CHD (p = 0.002) and increased end organ dysfunction (p = 0.04) compared to those with native valve. Fever was an almost universal symptom, associated in 23% of the episodes with heart failure. Staphylococcus aureus (25%) followed by coagulase-negative staphylococci (18%) and Streptococcus viridans (14%) were the most frequently isolated microorganisms, and three (7%) patients with central venous catheters had a fungal infection. Thromboembolic events were observed in 30% of the episodes, surgical intervention was required in 48% of cases. Mortality rate was 9%. Prosthetic material and CRP > 140 mg/L were independent predictors of complicated IE. CONCLUSIONS: Our findings emphasize the high morbidity of paediatric IE. The information provided could be useful for the identification of epidemiological and clinical profiles of children with IE and complicated forms.

Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018-2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20-0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018-2020 was 28% (P = 0.0001 for comparison with 2006-2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018-2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.

DTaP5-HBV-IPV-Hib pediatric hexavalent combination vaccine for use in children from 6 weeks through to 4 years of age.

Introduction: Combination vaccines reduce the number of injections received by children, hence improving timeliness and coverage, and general acceptability among caregivers and health-care providers. The most recent hexavalent vaccine, DTaP5-HBV-IPV-Hib, has been also approved by the FDA.Areas covered: DTaP5-HBV-IPV-Hib has demonstrated good immunogenic and safety profiles, not inferior to other hexavalent vaccines already in use in the European market. Either (2p+1/3p+1) immunization schedules can be used with no significant differences. A low incidence of severe adverse events has been shown, similar to other combination vaccines. No issues have arisen when concomitantly administered with other vaccines.Expert opinion: The inclusion of two additional acellular pertussis components (FIM2 and FIM3) might yield better protection against the disease, but this remains to be clinically proven. The new vaccine uses Hib with unique protein carrier (PRP-OMPC) which elicits higher earlier immune response without compromising safety. Compliance with the immunization schedules is expected to increase by decreasing the number of injections needed in combined vaccines for a single visit. In addition, the improvements on the ease-of-use by its liquid-formulation, makes the vaccine preparation more acceptable for use in clinics and may reduce the odds of administration errors.

Respiratory Syncytial Virus Seasonality: A Global Overview.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. By the age of 1 year, 60%-70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis, and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have failed to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.

New perspectives for hexavalent vaccines.

With the increase in the number of routine vaccinations the development of pentavalent and hexavalent combination vaccines fitting the routine vaccination schedules became a necessity. In this respect, Europe has taken the lead in comparison with other world regions, and routine vaccination with pentavalent and hexavalent combinations including DTPa, Hib, HepB and IPV has been on European vaccination programs for >15years. Since the marketing authorization of Hexavac® and Infanrix Hexa® in 2000, immunization schedules in most European countries have included hexavalent vaccines. In the last years, two new hexavalent vaccines have been licensed and commercialized worldwide. This paper presents a review of the pharmaceutical profiles of the three hexavalent vaccines currently available. In addition, we aim to review safety, co-administration, tolerability and other practical concerns of their use.

Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease.

Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) gene OR13C5 as the best candidate variant (P-value = 1.16 × 10-12; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1, HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR gene OR8U1/OR8U8, the taste receptor TAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.

Fallo hepático por intoxicación con producto casero elaborado con anís estrellado y anís verde en lactante de 4 meses / Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant

Las intoxicaciones en edad pediátrica representan una causa frecuente de consulta en urgencias hospitalarias. Los productos elaborados con hierbas pueden resultar tóxicos para el lactante. Se han descrito ampliamente las propiedades neurotóxicas del anís estrellado (Illicium verum), producto clásicamente empleado para el tratamiento del cólico del lactante. La presentación de fallo hepático agudo por consumo de infusiones elaboradas con hierbas de anís es excepcional en nuestro entorno. Se describe el caso de un lactante de 4 meses con hipertransaminasemia, coagulopatía grave, hipoglucemia no cetósica, acidosis metabólica moderada y síntomas neurológicos con crisis convulsivas y nistagmo. Tras descartar etiología infecciosa, metabólica y autoinmune y realizar una anamnesis cuidadosa, la familia refería haber administrado al paciente durante los últimos dos meses una infusión diaria con anís estrellado y anís verde (Pimpinella anisum). Es de gran importancia resaltar el grave riesgo de administrar infusiones de hierbas caseras en el lactante (AU)

Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum) have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum) infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants (AU)

Paradoxical reaction in immunocompetent children with tuberculosis.

BACKGROUND: A paradoxical reaction (PR) during anti-tuberculosis treatment is a phenomenon that is poorly studied in immunocompetent children. It is defined as a clinical or radiological worsening of pre-existing tuberculosis (TB) disease. METHODS: A retrospective descriptive study of children younger than 14 years of age was performed; these children developed PR during the years 2009 to 2014, following a diagnosis of TB. Demographic characteristics, microbiological results, treatment and outcome data were collected. RESULTS: Of 51 children diagnosed with TB, five (9.8%) developed a PR; four of these children had pulmonary TB and the remaining patient had miliary TB with central nervous system involvement. The PR occurred at a median of 42 days (range 23-53 days) after initiating therapy. Corticosteroids were started when PR was suspected, at a median dose of 1mg/kg/day. Clinical and radiological improvement was noted in all cases, with a median clinical regression time of 10.5 days (range 3-15 days) and a median radiological regression time of 45 days (range 26-105 days). No sequelae were described in any patient. CONCLUSIONS: PR in immunocompetent children during anti-tuberculosis treatment is not such an unusual reaction. Treatment with corticosteroids may be useful for the resolution of PR.

Prognosis of atypical teratoid rhabdoid tumors (AT/RT) treated with multimodal therapy protocols. Report of our series / Pronóstico de los tumores teratoides rabdoides atípicos (TT/RA) tratados con protocolos de terapia multimodal. Descripción de nuestra serie

Objective: Atypical teratoid rhabdoid tumors (AT/RT) of the central nervous system are rare, very aggressive embryological tumors, typically diagnosed in young patients and having a low survival rate after diagnosis. The aim of this study was to emphasize, based on the latest results in the literature, the need for protocols for multidisciplinary treatment in these patients. Material and methods: We report our series of 3 cases treated, diagnosed and followed up between 2009 and 2014. They were treated with multimodal therapy protocols (Rhabdoid SIOP-2007 and European Rhabdoid Registry EU-RHAB-2010). In addition, we carried out a literature review. Results: Two of our 3 cases (supratentorial and spinal tumors) did not show any progression of the disease after long follow-up, in contrast with most of the cases available in the literature. The second patient had a shorter survival. Conclusions: Patient age at the time of diagnosis, supratentorial location of the mass and fewer complications with adjuvant treatments seem to be factors yielding good prognosis for AT/RT tumors. In agreement with the latest international protocols, multidisciplinary treatment is the ideal treatment, consisting of radiotherapy and chemotherapy after complete tumor resection

Objetivo: Los tumores teratoides rabdoides atípicos (TT/RA) del sistema nervioso central son tumores embrionarios muy agresivos, de baja incidencia, típicamente diagnosticados en pacientes jóvenes, con una baja supervivencia tras el diagnóstico. El objetivo de este estudio es resaltar la necesidad del tratamiento multidisciplinar protocolizado de estos pacientes sobre la base de los resultados más actuales de la literatura. Material y métodos: Presentamos nuestra serie de 3 casos de TT/RA diagnosticados, tratados y seguidos entre 2009 y 2014. Nuestros pacientes se trataron siguiendo los protocolos de terapia multimodal (Rhabdoid SIOP-2007, European Rhabdoid Registry EU-RHAB-2010). De forma adicional, se realizó una revisión de la literatura. Resultados: Dos de nuestros pacientes (lesiones supratentorial y espinal) no presentaron progresión de la enfermedad años tras el diagnóstico, en comparación con lo descrito en la literatura. Por otra parte, el segundo paciente presentó una supervivencia menor. Conclusiones: Pueden considerarse factores de buen pronóstico: la edad del paciente en el momento del diagnóstico, las lesiones supratentoriales, y las escasas complicaciones de los tratamientos adyuvantes. El consenso actual en cuanto al tratamiento idóneo consiste en cirugía, seguida de quimioterapia y radioterapia

Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant.

Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum) have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum) infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants.

Prognosis of atypical teratoid rhabdoid tumors (AT/RT) treated with multimodal therapy protocols. Report of our series.

OBJECTIVE: Atypical teratoid rhabdoid tumors (AT/RT) of the central nervous system are rare, very aggressive embryological tumors, typically diagnosed in young patients and having a low survival rate after diagnosis. The aim of this study was to emphasize, based on the latest results in the literature, the need for protocols for multidisciplinary treatment in these patients. MATERIAL AND METHODS: We report our series of 3 cases treated, diagnosed and followed up between 2009 and 2014. They were treated with multimodal therapy protocols (Rhabdoid SIOP-2007 and European Rhabdoid Registry EU-RHAB-2010). In addition, we carried out a literature review. RESULTS: Two of our 3 cases (supratentorial and spinal tumors) did not show any progression of the disease after long follow-up, in contrast with most of the cases available in the literature. The second patient had a shorter survival. CONCLUSIONS: Patient age at the time of diagnosis, supratentorial location of the mass and fewer complications with adjuvant treatments seem to be factors yielding good prognosis for AT/RT tumors. In agreement with the latest international protocols, multidisciplinary treatment is the ideal treatment, consisting of radiotherapy and chemotherapy after complete tumor resection.