Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.

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.

Cystic echinococcosis in a Moroccan boy: a silent and neglected disease among refugee and migrant children.

We report the unusual case of a 5-year-old migrant boy from a rural area of Morocco with an almost-giant lung hydatid cyst that was an incidental finding on a chest X-ray performed during routine visa procedures. Echinococcus granulosus serology test was initially negative with subsequent positive seroconversion. Albendazole was started at 4 weeks before surgery and maintained for 4 months, with a favourable outcome. Cystic echinococcosis (CE) is considered a neglected tropical disease and affects more than one million people worldwide, mostly from a lower socioeconomic background. Preventive measures have been limited in underdeveloped regions. Children with CE are especially vulnerable, due not only to the high pathogenic potential of the disease but also to their frequent involvement in challenging socioeconomic situations, including migration. The incidence of CE is increasing in Europe because of high immigration flows from endemic countries. Nevertheless, CE is not covered by current migrant screening protocols.

Distinct Laboratory and Clinical Features of Secondary Hemophagocytic Lymphohistiocytosis in Pediatric Visceral Leishmaniasis: A Retrospective Analysis of 127 Children in Andalusia, Spain (2004-2019).

BACKGROUND: Visceral leishmaniasis (VL) is an endemic in Southern Europe. However, details regarding disease burden, clinical presentations, laboratory markers, management and outcome in children are scarce. METHODS: Medical records of children (<14 years) admitted with VL to 10 pediatric units in Andalusia (2004-2019) were retrospectively reviewed. VL diagnosis was based on clinical presentation, serology, microscopy and molecular methods. Diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was established using the hemophagocytic lymphohistiocytosis-2004 criteria. RESULTS: A total of 127 patients were identified. Median age was 14.5 months; the main clinical presentations were fever and splenomegaly (95.3% each). Cytopenias were the most common laboratory abnormalities. Diagnostics as well as treatment regimens varied over time and the participating centers. Liposomal amphotericin B was prescribed in 97.6%; relapses as well as adverse events were rarely observed (3.1% each). Thirty-seven patients, diagnosed with sHLH required longer hospital admission (P = 0.001), an increased number of platelet (P < 0.006) and red blood cell (P = 0.0001) transfusions and pediatric intensive care unit admission (P = 0.007). Monocytopenia (P = 0.011) and high C-reactive protein levels (P = 0.031), variables not included in the hemophagocytic lymphohistiocytosis-2004 criteria, were associated with sHLH. One patient deceased in the context of the Leishmania infection. CONCLUSIONS: We report data on the largest pediatric VL cohort from Europe, commonly associated with sHLH. Raised C-reactive protein levels and monocytopenia appear to be associated with sHLH. The latter may help to identify these patients and to guide decisions regarding need of additional supportive clinical care and immunomodulatory therapies. The observed high rate of heterogeneity in terms of diagnosis and management warrants the establishment of appropriate guidelines.

¿Es posible ofrecer un algoritmo de decisión clínica en la enfermedad COVID-19 en Atención Primaria? / Is it possible to offer a clinical decision algorithm in COVID-19 disease in Primary Care?

Hasta ahora, los datos recogidos en los casos de procesos clínicos provocados por el coronavirus SARS-CoV-2 (COVID-19) en niños sugieren que son cuadros leves en comparación con las infecciones en pacientes adultos; no obstante, se ha informado de casos graves, como el síndrome inflamatorio multisistémico (SIM), que precisa de valoración y actuación de emergencia. En el contexto de la consulta del pediatra de Atención Primaria y coincidiendo con el inicio del curso escolar, en una época en la que habitualmente aumenta la incidencia de procesos como la gripe, infección por el virus respiratorio sincitial (VRS) y otros cuadros respiratorios, es habitual la demanda por síntomas que pueden hacer sospechar cualquiera de estas infecciones. En este sentido, es importante llegar a un diagnóstico que permita el manejo más adecuado del paciente. Epidemiológicamente, de manera que se pueda disminuir la transmisión comunitaria tomando las medidas adecuadas y clínicamente para así poder ponderar el nivel de gravedad y poner en marcha las actuaciones más adecuadas. Dado que no existen escalas válidas que ofrezcan un puntaje para valorar cuál es la actuación más adecuada ante la sospecha de una infección COVID-19, planteamos los beneficios de un algoritmo de decisión clínica que tiene en cuenta las connotaciones epidemiológicas, basado en la gravedad clínica, para ofrecer la atención clínica más adecuada a los pacientes

So far, the data collected in the cases of clinical processes caused by the SARS-CoV-2 (COVID-19) coronavirus in children suggest that they are mild compared to infections in adult patients; However, serious cases such as multisystemic inflammatory syndrome (SIM) have been reported, which requires assessment and emergency action. In the context of the of the Primary Care pediatrician consultation and coinciding with the beginning of the school year, at a time when the incidence of influenza, RSV infection and other respiratory conditions usually increases, consultations for symptoms that can lead to suspect these infections. Therefore, it is important to reach a diagnosis that allows the most appropriate management of the patient and decreasing the community transmission by taking pertinent measures. Given that there are no valid scales that offer a score to assess which is the most appropriate action in the event of a suspected COVID-19 infection, we propose the benefits of a clinical decision algorithm that takes into account epidemiological connotations, based on clinical severity to offer the most appropriate clinical care to patients

Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases. Clinical manifestations of PID can be fatal or leave sequelae that worsen the quality of life of patients. Traditionally, the treatment of PIDs has been largely supportive, with the exception of bone marrow transplantation and, more recently, gene therapy. The discovering of new affected pathways, the development of new molecules and biologics, and the increasing understanding of the molecular basis of these disorders have created opportunities in PIDs therapy. This document aims to review current knowledge and to provide recommendations about the diagnosis and clinical management of adults and children with PIDs based on the available scientific evidence taking in to account current practice and future challenges. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation where available.