Dampening of IL-2 Function in Infants With Severe Respiratory Syncytial Virus Disease.

Background: FOXP3+ regulatory T cells (Tregs) restrain the destructive potential of the immune system. We have previously reported a pronounced reduction in circulating Tregs in infants with severe respiratory syncytial virus (RSV) disease. Because interleukin-2 (IL-2) is critical for Treg growth, survival, and activity, we here analyzed IL-2 production and function in RSV-infected infants. Methods: Phenotype, proliferation, IL-2 production, and IL-2 signaling in CD4+ T cells were analyzed by flow cytometry. Serum soluble CD25 levels were quantified by ELISA. Results: CD4+ T cells from RSV-infected infants produced lower amounts of IL-2 and showed a reduced proliferative response compared with healthy infants. IL-2 increased CD4+ T-cell proliferation and FOXP3 expression in both healthy and RSV-infected infants. However, although IL-2 induced a similar pattern of STAT5 phosphorylation, the proliferative response of CD4+ T cells and the expression of FOXP3+ remained significantly lower in RSV-infected infants. Interestingly, we found a negative correlation between disease severity and both the production of IL-2 by CD4+ T cells and the ability of exogenous IL-2 to restore the pool of FOXP3+CD4+ T cells. Conclusions: A reduced ability to produce IL-2 and a limited response to this cytokine may affect the function of CD4+ T cells in RSV-infected infants.

Respiratory Syncytial Virus (RSV) Infects CD4+ T Cells: Frequency of Circulating CD4+ RSV+ T Cells as a Marker of Disease Severity in Young Children.

BACKGROUND: Although human airway epithelial cells are the main target of respiratory syncytial virus (RSV), it also infects immune cells, such as macrophages and B cells. Whether T cells are permissive to RSV infection is unknown. We sought to analyze the permissiveness of CD4+ T cells to RSV infection. METHODS: CD4+ and CD8+ T cells from cord blood, healthy young children, and adults were challenged by RSV or cocultured with infected HEp-2 cells. Infection, phenotype, and cytokine production by T cells were analyzed by flow cytometry or enzyme-linked immunosorbent assay. Expression of RSV antigens by circulating CD4+ T cells from infected children was analyzed by flow cytometry, and disease severity was defined by standard criteria. RESULTS: CD4+ and CD8+ T cells were productively infected by RSV. Infection decreased interleukin 2 and interferon γ production as well as the expression of CD25 and Ki-67 by activated CD4+ T cells. Respiratory syncytial virus antigens were detected in circulating CD4+ and CD8+ T cells during severe RSV infection of young children. Interestingly, the frequency of CD4+ RSV+ T cells positively correlated with disease severity. CONCLUSIONS: Respiratory syncytial virus infects CD4+ and CD8+ T cells and compromises T-cell function. The frequency of circulating CD4+ RSV+ T cells might represent a novel marker of severe infection.

ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.

Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection. Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed. Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency. Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.

Fcγ Receptor IIa (FCGR2A) Polymorphism Is Associated With Severe Respiratory Syncytial Virus Disease in Argentinian Infants.

Background: Most patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease. Methods: Blood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied. Results: Genotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3. Conclusions: We found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization.

High-flow nasal cannula oxygen therapy in infants with acute lower respiratory tract infection. An experience in hospitals of the City of Buenos Aires.

INTRODUCTION: During the winter, infants with acute lower respiratory tract infection (ALRTI) overburden health resources. In the Autonomous City of Buenos Aires, 35 000 children are seen at the hospitals every year; 8-10 % of them are admitted to the general hospitalization ward and 5-12 % of these, to the intensive care unit (ICU). In 2017, the Department of Maternal and Child Health of the Autonomous City of Buenos Aires included high flow nasal cannula (HNFC) oxygen therapy in the ALRTI protocol in the general ward of 3 hospitals. The objective of this study was to describe its outcomes and explore the potential factors related to therapeutic failure. METHODS: Prospective, descriptive study with infants < 18 months old hospitalized due to ALRTI in 3 hospitals (Durand, Elizalde, Gutiérrez) between June and September 2017. All children unable to comply with low-flow therapeutic targets received HNFC oxygen therapy; admission to the ICU was considered a failure. RESULTS: Out of 522 patients hospitalized due to ALRTI, 39.7% required HNFC oxygen therapy. No significant baseline differences were observed between patients receiving HNFC and conventional oxygen therapy. Failure was observed in only 8.7% of patients with HNFC oxygen therapy. The decrease in respiratory rate was significantly greater and longer in patients with support success versus those with failure (p < 0.01). No complications were recorded. CONCLUSIONS: The implementation of HNFC oxygen therapy under a protocol in the general wards was a safe measure. Patients with therapeutic failure showed a smaller reduction in respiratory rate during treatment.

Introducción. Durante el invierno, los lactantes con infecciones respiratorias agudas bajas (IRAB) sobrecargan los recursos sanitarios. En la Ciudad Autónoma de Buenos Aires, 35 000 niños son asistidos anualmente en hospitales; se interna el 8-10 % en unidades generales, y el 5-12 % de ellos, en unidades de terapia intensiva. En 2017, el Departamento de Salud Materno-Infantil de dicha ciudad incluyó la oxigenoterapia por cánula nasal de alto flujo (CNAF) en el protocolo IRAB en unidades generales de tres hospitales. El objetivo de este trabajo es describir los resultados y explorar potenciales factores relacionados con el fracaso terapéutico. Métodos. Estudio prospectivo descriptivo que incluyó a lactantes < 18 meses hospitalizados por IRAB en 3 hospitales (Durand, Elizalde, Gutiérrez), de junio a septiembre de 2017. Todos los niños incapaces de cumplir los objetivos terapéuticos con bajo flujo recibieron CNAF, y se consideró fracaso de soporte el ingreso a Terapia Intensiva. Resultados. De 522 pacientes hospitalizados por IRAB, el 39,7 % requirieron CNAF. No se observaron diferencias basales significativas entre pacientes con CNAF y con oxigenoterapia convencional. Solo el 8,7 % de los pacientes con CNAF presentaron fracaso. Los pacientes con éxito del soporte mostraron un descenso de la frecuencia respiratoria significativamente mayor y más sostenido en el tiempo que aquellos con fracaso (p < 0,01). No se registraron complicaciones. Conclusión. La implementación protocolizada de CNAF en unidades generales fue una medida segura. Los pacientes con fracaso del soporte mostraron una menor disminución en la frecuencia respiratoria a lo largo del tratamiento.

Postdiarrhoeal haemolytic uraemic syndrome without thrombocytopenia. / Síndrome urémico hemolítico asociado a diarrea sin trombocitopenia.

BACKGROUND: Thrombocytopenia is a hallmark of postdiarrhoeal haemolytic uraemic syndrome (D+ HUS), although it can be transient and therefore undetected. There is scarce information regarding the prevalence and the course of the disease in children with D+ HUS without thrombocytopenia. OBJECTIVE: To determine the prevalence of D+ HUS without thrombocytopenia and to describe the clinical characteristics of a series of children with this condition. PATIENTS AND METHODS: The medical records of patients with D+ HUS hospitalised between 2000 and 2016 were reviewed to identify those without thrombocytopenia (>150,000mm3). Demographic, clinical and laboratory parameters of the selected cases were collected and descriptively analysed. RESULTS: Nine cases (5.6%) without thrombocytopenia were identified among 161 patients hospitalised during the study period. Median age at diagnosis was 17 months (7-32) and median prodromal symptom duration was 15 days (7-21). Eight patients maintained normal urine output while the remaining one required dialysis. No patient presented with severe extrarenal compromise and/or hypertension. CONCLUSIONS: The prevalence of non-thrombocytopenic D+ HUS was 5.6% and most cases occurred with mild forms of the disease; however, the need for dialysis in one of them indicated that normalisation of platelet count is not always an accurate marker for disease remittance. Our results also confirm that the time of onset of D+ HUS in patients without thrombocytopenia is usually delayed with respect to the initial intestinal symptoms; thus, heightened diagnostic suspicion is necessary.

[Childhood pemphigus vulgaris, a case report]. / Pénfigo vulgar de la infancia, a propósito de un caso.

Pemphigus vulgaris is a chronic disease that is characterized by flaccid blisters and erosions, caused by immunoglobulin G autoantibodies against epidermal components. It is highly unusual in the pediatric population; it represents the 1.4 - 2.9% of the total cases. We present a case of pemphigus vulgaris in a 12 year old girl, which has implied a challenge both in its diagnosis and in its treatment.

El pénfigo vulgar es una enfermedad crónica que se caracteriza por ampollas fláccidas y erosiones, causadas por un fenómeno autoinmune con autoanticuerpos inmunoglobulina G circulantes contra componentes de la epidermis. Su presentación en la infancia es altamente infrecuente; representa el 1,4%-2,9% de todos los casos de pénfigo vulgar. Presentamos un caso de pénfigo vulgar en una niña de 12 años, que implicó un desafío en su diagnóstico y terapéutica.

Consenso sobre el tratamiento del síndrome inflamatorio multisistémico asociado a COVID-19 / Consensus on treatment of multisystemic inflammatory syndrome associated with COVID-19

La pandemia ocasionada por el nuevo coronavirus (SARS-CoV-2), declarada por la Organización Mundial de la Salud OMS) en marzo de 2020, afecta a un reducido número de pacientes pediátricos, quienes presentan, en su mayoría, compromiso respiratorio leve y evolución favorable. Sin embargo, en niños previamente sanos, comenzó a observarse un aumento de casos definidos como síndrome inflamatorio multisistémico (SIM-C) o similar a Kawasaki (Kawasaki-like) asociado a la enfermedad por el nuevo coronavirus (COVID-19) (KL-C) que evolucionan al shock y requieren internación en la unidad de cuidados intensivos.Los cuadros de SIM-C y los KL-C se caracterizan por fiebre, signos de inflamación, síntomas gastrointestinales y disfunción cardiovascular; las formas graves de presentación tienen mayor incidencia de hipotensión y/o shock. En el laboratorio se observan marcadores de inflamación, hipercoagulabilidad y daño miocárdico. El tratamiento farmacológico de primera línea consiste en la administración de inmunoglobulina por vía intravenosa más ácido acetilsalicílico por vía oral.Se recomienda un abordaje multidisciplinario para un diagnóstico certero y un tratamiento temprano y eficaz para disminuir la morbimortalidad.

The pandemic caused by the SARS-CoV-2 virus declared by the WHO in March 11th 2020, affects a small number of pediatric patients, who mostly present mild respiratory compromise and favorable evolution.However began to be observed in previously healthy children, an increase in cases defined as "Multisystemic Inflammatory Syndrome" (MIS-C) or "Kawasaki-like" post-COVID 19 (KL-C) that evolve to shock and require hospitalization in the Pediatric Intensive Care Unit.MIS-C and KL-C are characterized by fever; signs of inflammation, gastrointestinal symptoms, and cardiovascular dysfunction, associated with sever forms of presentation with higher incidence of hypotension and/or shock. In the laboratory, markers of inflammation, hypercoagulability and myocardial damage are observed. First-line drug treatment consists of intravenous immunoglobulin plus oral acetylsalicylic acid.A multidisciplinary approach is recommended for an accurate diagnosis and an early and effective treatment, in order to reduce morbidity and mortality.

Oxigenoterapia con cánula nasal de alto flujo en lactantes con infección respiratoria baja aguda: Experiencia en hospitales de la Ciudad de Buenos Aires / High-flow nasal cannula oxygen therapy in infants with acute lower respiratory tract infection: An experience in hospitals of the City of Buenos Aires

Introducción. Durante el invierno, los lactantes con infecciones respiratorias agudas bajas (IRAB) sobrecargan los recursos sanitarios. En la Ciudad Autónoma de Buenos Aires, 35 000 niños son asistidos anualmente en hospitales; se interna el 8-10 % en unidades generales, y el 5-12 % de ellos, en unidades de terapia intensiva. En 2017, el Departamento de Salud Materno-Infantil de dicha ciudad incluyó la oxigenoterapia por cánula nasal de alto flujo (CNAF) en el protocolo IRAB en unidades generales de tres hospitales. El objetivo de este trabajo es describir los resultados y explorar potenciales factores relacionados con el fracaso terapéutico. Métodos. Estudio prospectivo descriptivo que incluyó a lactantes < 18 meses hospitalizados por IRAB en 3 hospitales (Durand, Elizalde, Gutiérrez), de junio a septiembre de 2017. Todos los niños incapaces de cumplir los objetivos terapéuticos con bajo flujo recibieron CNAF, y se consideró fracaso de soporte el ingreso a Terapia Intensiva. Resultados. De 522 pacientes hospitalizados por IRAB, el 39,7 % requirieron CNAF. No se observaron diferencias basales significativas entre pacientes con CNAF y con oxigenoterapia convencional. Solo el 8,7 % de los pacientes con CNAF presentaron fracaso. Los pacientes con éxito del soporte mostraron un descenso de la frecuencia respiratoria significativamente mayor y más sostenido en el tiempo que aquellos con fracaso (p < 0,01). No se registraron complicaciones. Conclusión. La implementación protocolizada de CNAF en unidades generales fue una medida segura. Los pacientes con fracaso del soporte mostraron una menor disminución en la frecuencia respiratoria a lo largo del tratamiento.

Introduction. During the winter, infants with acute lower respiratory tract infection (ALRTI) overburden health resources. In the Autonomous City of Buenos Aires, 35 000 children are seen at the hospitals every year; 8-10 % of them are admitted to the general hospitalization ward and 5-12 % of these, to the intensive care unit (ICU). In 2017, the Department of Maternal and Child Health of the Autonomous City of Buenos Aires included high flow nasal cannula (HNFC) oxygen therapy in the ALRTI protocol in the general ward of 3 hospitals. The objective of this study was to describe its outcomes and explore the potential factors related to therapeutic failure. Methods. Prospective, descriptive study with infants < 18 months old hospitalized due to ALRTI in 3 hospitals (Durand, Elizalde, Gutiérrez) between June and September 2017. All children unable to comply with low-flow therapeutic targets received HNFC oxygen therapy; admission to the ICU was considered a failure. Results. Out of 522 patients hospitalized due to ALRTI, 39.7% required HNFC oxygen therapy. No significant baseline differences were observed between patients receiving HNFC and conventional oxygen therapy. Failure was observed in only 8.7% of patients with HNFC oxygen therapy. The decrease in respiratory rate was significantly greater and longer in patients with support success versus those with failure (p < 0.01). No complications were recorded. Conclusion. The implementation of HNFC oxygen therapy under a protocol in the general wards was a safe measure. Patients with therapeutic failure showed a smaller reduction in respiratory rate during treatment.

[Pott puffy tumor: case report]. / Tumoración de Pott: A propósito de un caso.

We present the case of a child with frontal sinusitis, who also suffers from a severe intracranial disease. Although sinusitis intracranial issues are rare nowadays, they include a wide range of serious entities such as meningitis, brain abscesses and thrombosis of the cavernous sinus. We emphasize the importance of early diagnosis and an adequate initial empirical treatment to prevent possible complications. Once they are presented, an aggressive surgical medical treatment is required for its resolution.

[Norwegian scabies in a pediatric patient with Down syndrome, a case report]. / Sarna noruega en un paciente pediátrico con síndrome de Down: A propósito de un caso.

Norwegian (crusted) scabies is a rare and extreme manifestation of scabies that can be observed mainly among immunosuppressed patients. Due to the high number of scabies mites present in each lesion, crusted scabies symptoms are much more intense than in usual scabies and it is thus highly contagious. A case study of a child with Down syndrome and Norwegian scabies who shows a good response to a treatment combining keratolytics, emollients, ivermectin and topical scabicides is described.

Tumoración de Pott: A propósito de un caso / Pott puffy tumor: Case report

Se analiza el caso de un niño con sinusitis frontal, con una forma de presentación poco habitual que, además, padecía una complicación intracraneal grave. Las complicaciones intracraneales de las sinusitis son raras en cerebrales y trombosis del seno cavernoso. Se hace hincapié en la importancia del diagnóstico precoz y de un tratamiento empírico inicial adecuado para evitar las posibles complicaciones. Asimismo, cabe enfatizar que una vez producidas estas, requieren un tratamiento médico-quirúrgico intensivo para su resolución.

We present the case of a child with frontal sinusitis, who also suffers from a severe intracranial disease. Although sinusitis intracranial issues are rare nowadays, they include a wide range of serious entities such as meningitis, brain abscesses and thrombosis of the cavernous sinus. We emphasize the importance of early diagnosis and an adequate initial empirical treatment to prevent possible complications. Once they are presented, an aggressive surgical medical treatment is required for its resolution.

Sarna noruega en un paciente pediátrico con síndrome de Down: A propósito de un caso / Norwegian scabies in a pediatric patient with Down syndrome, a case report

La sarna noruega es una variedad muy infrecuente¹ de la escabiosis que afecta principalmente a pacientes inmunodeprimidos. Debido a la gran cantidad de parásitos presentes en las lesiones, las manifestaciones clínicas son mucho más intensas que en las formas habituales de sarna y es altamente contagiosa. Se describe el caso de un niño con síndrome de Down con este tipo de parasitosis, que presentó una respuesta muy satisfactoria al tratamiento combinado con queratolíticos, emolientes, ivermectina y acaricidas tópicos.

Norwegian (crusted) scabies is a rare and extreme manifestation of scabies that can be observed mainly among immunosuppressed patients. Due to the high number of scabies mites present in each lesion, crusted scabies symptoms are much more intense than in usual scabies and it is thus highly contagious. A case study of a child with Down syndrome and Norwegian scabies who shows a good response to a treatment combining keratolytics, emollients, ivermectin and topical scabicides is described.

Síndrome urémico hemolítico asociado a infección por Shigella flexneri / Haemolytic Uraemic Syndrome (Martin Bell): cytogenetical study vs molecular biology techniques

Niña de 9 años de edad de deficiente medio socio-económico con mal estado nutricional.Inició su enfermedad con dolor abdominal,vómitos y diarrea.Tratada en un centro periférico con TMS presentó episodio convulsivo por lo que la derivaron a nuestro hospital.Ingresó gravemente enferma con letargo,palidez e ictericia,hemesturia macroscópica con cilindruria,proteinuria e isostenuria y cuadro de púrpura con trombocitopenia,esquizocitos e insuficiencia renal.Se plantearon como diagnósticos diferenciales:síndrome urémico hemolítico,púrpura trobótica trombocitopénica,leptospirosis,fiebre hemorrágica argentina,lupus erimatoso sistémico y sepsis.Serología para leptospirosis y fiebre hemorrágica argentina,FAN,anti ADN,factor reumatoideo,reacción de Widal y anticuerpos anti-veroxitina 1 y verotoxina 2 fueron todos negativos en tanto el coprocultivo desarrolló Shigella flexneri.Se efectuó plasmaférisis y transfusión de sedimiento globular.A partir del quinto día comenzó a recuperarse normalizanso su cuadro hematológico y humoral.La biopsis renal efectuada a los 17 días de evolución inmediatamente antes del alta mostró lesiones compatibles con síndrome urémico hemolítico en regresión.La edad,el estado nutritivo y las condiciones socio-ambientales son diferentes a lo observado en el síndrome urémico hemolítico endemoepidémico de nuestro país,generalmente asociado a infección por gérmenes productores de verotoxina.No se estudiaron citotoxinas en materia fecal pero anticuerpos anti-veroxina resultaron negativos,El resultado de coprocultivo y la bipsia renal muestran el síndrome urémico hemolítico como asociado a infección por Shigella flexneri,lo cual no ha sido referido hasta la fecha en nuestro país