Overnutrition, Nasopharyngeal Pathogenic Bacteria and Proinflammatory Cytokines in Infants with Viral Lower Respiratory Tract Infections.

Background: Little is known about the interaction between the nasopharyngeal bacterial profile and the nutritional status in children. In this study, our main goal was to evaluate the associations between overnutrition and the presence of four potentially pathogenic bacteria in the nasopharynx of infants with viral lower respiratory tract infections (LRTI). In addition, we determined whether changes in the nasopharyngeal bacterial profile were associated with mucosal and serum proinflammatory cytokines and with clinical disease severity. Methods: We enrolled 116 children less than 2 years old hospitalized for viral LRTI during two consecutive respiratory seasons (May 2016 to August 2017); their nutritional status was assessed, and nasopharyngeal and blood samples were obtained. S. aureus, S. pneumoniae, H. influenzae, M. catarrhalis, and respiratory viruses were identified in nasopharyngeal samples by qPCR. Cytokine concentrations were measured in nasopharyngeal and blood samples. Disease severity was assessed by the length of hospitalization and oxygen therapy. Results: Nasopharyngeal pathogenic bacteria were identified in 96.6% of the enrolled children, and 80% of them tested positive for two or more bacteria. The presence and loads of M. catarrhalis was higher (p = 0.001 and p = 0.022, respectively) in children with overnutrition (n = 47) compared with those with normal weights (n = 69). In addition, the detection of >2 bacteria was more frequent in children with overnutrition compared to those with normal weight (p = 0.02). Multivariate regression models showed that the presence and loads of S. pneumoniae and M. catarrhalis were associated with higher concentrations of IL-6 in plasma and TNF-α in mucosal samples in children with overnutrition. Conclusions: The nasopharyngeal profile of young children with overnutrition was characterized by an over representation of pathogenic bacteria and proinflammatory cytokines.

Hematological abnormalities in immunosuppressed patients with COVID-19: Evidence from a single center. A cross sectional study.

BACKGROUND: Changes in hematological parameters in patients with COVID-19 are emerging as important features of the disease in the general population. In the present study we aimed to explore the hematological characteristics and its prevalence proportion ratio in patients with immunosuppression with COVID-19. AIM: To explore the differences between immunosuppressed and non-immunosuppressed patients, with and without COVID-19 from a hematological perspective. METHODS: This cross-sectional study reports on the baseline complete blood count in patients attending the HHA Hospital, in Chile. The study reports descriptive characteristics of the population, including sex, age, ethnicity, corticoids and biological therapy scheme and a complete report of blood test results. A total of 476 patients were enrolled in this study from October of 2020 to April 2021. RESULTS: Findings revels a significant increment (p value ≤ 0.001) on the median of total neutrophils and leucocytes, and in platelet-lymphocyte ratio (PLR), neutrophil- lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) in immunosuppressed patients with COVID-19 (IS(+)) and immunocompetent patients with COVID-19 (IC(+)) compared with their respective controls. By contrast, a significant reduction on the median of lymphocytes, and eosinophiles was observed in IS(+) individuals compared with its controls. Also, the red blood cell count, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration were significantly reduced in IS(+) patients, whereas red blood cell, distribution width and mean corpuscular volume, were significantly higher in patients with COVID-19. CONCLUSION: Rapid blood tests, including, neutrophil, lymphocytes count and PLR, NLR can be used for early assessment and management of patients with immunosuppression.

Pneumococcal vaccine in patients with idiopathic juvenile arthritis in treatment with tumor necrosis factor inhibitors.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood. The therapy with tumor necrosis factor (TNF) inhibitors (TNFi) in JIA patients has demonstrated efficacy and safety. The most reported adverse event is the high susceptibility to infections. Preventive vaccination helps to decrease these risks. The information on response to vaccines in JIA patients having treatment with anti-TNF is limited. OBJECTIVES: To evaluate the response to pneumococcal vaccine in JIA patients undergoing treatment with mAb. MATERIALS AND METHODS: Analytical observational mixed cohort study. Data obtained from the clinical records of an immunorheumatology polyclinic of a metropolitan hospital in Santiago (Chile). Treatments, pneumococcal vaccine schedules, immunological laboratory, and measurement of specific antibodies against 10 pneumococcal serotypes were recorded. RESULTS: Nineteen patients were included; average age was 13.8 years; and average evolution time of the disease was 46.2 months. Adalimumab (Humira®) was indicated in case of 13 patients (68.4%) and etanercept (Enbrel®) to 6 (31.5%). The most indicated scheme was a dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed at 8 weeks by a dose of pneumococcal polysaccharide vaccine (PPSV23) in nine (47.3%) patients. Seventeen (89.4%) patients were on immunosuppressive treatment at the time of vaccination. Only one patient did not meet the criteria for response to vaccine. CONCLUSIONS: The pneumococcal vaccine induces protective levels of serum antibodies in JIA patients undergoing TNFi treatment. The vaccination schedule and the lymphocyte count could influence the response capacity.

Pneumococcal vaccine in patients with idiopathic juvenile arthritis in treatment with tumor necrosis factor inhibitors

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood. The therapy with tumor necrosis factor (TNF) inhibitors (TNFi) in JIA patients has demonstrated efficacy and safety. The most reported adverse event is the high susceptibility to infections. Preventive vaccination helps to decrease these risks. The information on response to vaccines in JIA patients having treatment with anti-TNF is limited. Objectives: To evaluate the response to pneumococcal vaccine in JIA patients undergoing treatment with mAb. Materials and methods Analytical observational mixed cohort study. Data obtained from the clinical records of an immunorheumatology polyclinic of a metropolitan hospital in Santiago (Chile). Treatments, pneumococcal vaccine schedules, immunological laboratory, and measurement of specific antibodies against 10 pneumococcal serotypes were recorded. Results: Nineteen patients were included; average age was 13.8 years; and average evolution time of the disease was 46.2 months. Adalimumab (Humira®) was indicated in case of 13 patients (68.4%) and etanercept (Enbrel®) to 6 (31.5%). The most indicated scheme was a dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed at 8 weeks by a dose of pneumococcal polysaccharide vaccine (PPSV23) in nine (47.3%) patients. Seventeen (89.4%) patients were on immunosuppressive treatment at the time of vaccination. Only one patient did not meet the criteria for response to vaccine. Conclusions: The pneumococcal vaccine induces protective levels of serum antibodies in JIA patients undergoing TNFi treatment. The vaccination schedule and the lymphocyte count could influence the response capacity (AU)

[Consolidated recommendations of the Advisory Committee on Vaccines and Immunization Strategies- on prioritizing COVID-19 vaccination]. / Consolidado de recomendaciones del Comité Asesor de Vacunas y Estrategias de Inmunización-CAVEI, sobre priorización de vacunación COVID-19.

COVID-19 is a global public health issue due to its epidemic nature that, to date, lacks pharmacological treatment. However, some COVID-19 vaccines have been authorized for emergency use, although the duration of their protection, their ability to interrupt viral transmission, and their efficacy against emerging variants of SARS-CoV-2 are being studied. Chile's SARS-CoV-2 vaccination campaign required design and planning, like any other campaign. This process included the prioritization of risk groups for vaccination given the limited supply of COVID-19 vaccines globally. Throughout 2020, CAVEI issued recommendations on the prioritization of population groups to be vaccinated against SARS-CoV-2 in response to different needs and in accordance with available evidence. These recommendations are consolidated in Table 1 in this report. In summary, it was recommended that healthcare workers, people in long-term residences and essential State personnel be vaccinated in phase 1. In phase 2, persons over 65 years of age and people with comorbidities. In phase 3, essential tasks workers and, lastly, the general population.

Consolidado de recomendaciones del Comité Asesor de Vacunas y Estrategias de Inmunización-CAVEI, sobre priorización de vacunación COVID-19 / Consolidated recommendations of the Advisory Committee on Vaccines and Immunization Strategies- on prioritizing COVID-19 vaccination

Resumen El COVID-19 es un problema de salud pública mundial por su carácter epidémico que, a la fecha, carece de tratamiento farmacológico. Sin embargo, ya se cuenta con algunas vacunas autorizadas para uso en emergencia, aunque la duración de su protección, su capacidad para interrumpir la transmisión viral y su eficacia frente a variantes emergentes de SARS-CoV-2 se encuentran en estudio. La campaña de vacunación contra SARS-CoV-2 de Chile requirió de diseño y planificación, como toda campaña. Parte de estos fue la priorización de grupos objetivo de vacunar, necesaria debido a que el mundo se vería enfrentado a un suministro limitado de vacunas COVID-19. En distintos momentos del año 2020, el CAVEI emitió recomendaciones sobre priorización de grupos de población a vacunar contra SARS-CoV-2, respondiendo a diferentes necesidades y según la evidencia disponible en cada instancia. Éstas se consolidan en la Tabla 1 de este informe. Resumidamente, en fase 1 se recomendó vacunar al personal de salud, residencias de larga estadía y personal crítico del Estado. En fase 2, a personas mayores de 65 años y población con comorbilidades. En fase 3, a personas que cumplen labores esenciales y, finalmente, a la población general.

Abstract COVID-19 is a global public health issue due to its epidemic nature that, to date, lacks pharmacological treatment. However, some COVID-19 vaccines have been authorized for emergency use, although the duration of their protection, their ability to interrupt viral transmission, and their efficacy against emerging variants of SARS-CoV-2 are being studied. Chile's SARS-CoV-2 vaccination campaign required design and planning, like any other campaign. This process included the prioritization of risk groups for vaccination given the limited supply of COVID-19 vaccines globally. Throughout 2020, CAVEI issued recommendations on the prioritization of population groups to be vaccinated against SARS-CoV-2 in response to different needs and in accordance with available evidence. These recommendations are consolidated in Table 1 in this report. In summary, it was recommended that healthcare workers, people in long-term residences and essential State personnel be vaccinated in phase 1. In phase 2, persons over 65 years of age and people with comorbidities. In phase 3, essential tasks workers and, lastly, the general population.

Exploring the Impact of Ketodeoxynonulosonic Acid in Host-Pathogen Interactions Using Uptake and Surface Display by Nontypeable Haemophilus influenzae.

Surface expression of the common vertebrate sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) by commensal and pathogenic microbes appears structurally to represent "molecular mimicry" of host sialoglycans, facilitating multiple mechanisms of host immune evasion. In contrast, ketodeoxynonulosonic acid (Kdn) is a more ancestral Sia also present in prokaryotic glycoconjugates that are structurally quite distinct from vertebrate sialoglycans. We detected human antibodies against Kdn-terminated glycans, and sialoglycan microarray studies found these anti-Kdn antibodies to be directed against Kdn-sialoglycans structurally similar to those on human cell surface Neu5Ac-sialoglycans. Anti-Kdn-glycan antibodies appear during infancy in a pattern similar to those generated following incorporation of the nonhuman Sia N-glycolylneuraminic acid (Neu5Gc) onto the surface of nontypeable Haemophilus influenzae (NTHi), a human commensal and opportunistic pathogen. NTHi grown in the presence of free Kdn took up and incorporated the Sia into its lipooligosaccharide (LOS). Surface display of the Kdn within NTHi LOS blunted several virulence attributes of the pathogen, including Neu5Ac-mediated resistance to complement and whole blood killing, complement C3 deposition, IgM binding, and engagement of Siglec-9. Upper airway administration of Kdn reduced NTHi infection in human-like Cmah null (Neu5Gc-deficient) mice that express a Neu5Ac-rich sialome. We propose a mechanism for the induction of anti-Kdn antibodies in humans, suggesting that Kdn could be a natural and/or therapeutic "Trojan horse" that impairs colonization and virulence phenotypes of free Neu5Ac-assimilating human pathogens.IMPORTANCE All cells in vertebrates are coated with a dense array of glycans often capped with sugars called sialic acids. Sialic acids have many functions, including serving as a signal for recognition of "self" cells by the immune system, thereby guiding an appropriate immune response against foreign "nonself" and/or damaged cells. Several pathogenic bacteria have evolved mechanisms to cloak themselves with sialic acids and evade immune responses. Here we explore a type of sialic acid called "Kdn" (ketodeoxynonulosonic acid) that has not received much attention in the past and compare and contrast how it interacts with the immune system. Our results show potential for the use of Kdn as a natural intervention against pathogenic bacteria that take up and coat themselves with external sialic acid from the environment.

Overnutrition in Infants Is Associated With High Level of Leptin, Viral Coinfection and Increased Severity of Respiratory Infections: A Cross-Sectional Study.

Objective: To investigate the relationship of overnutrition (obese and overweight) with severity of illness in children hospitalized with acute lower respiratory infections (ALRIs), frequency of viral coinfections and leptin levels. Methods: We studied 124 children <2 years old that were hospitalized for ALRI. Nutritional status was calculated by z-scores according to weight-for-age z-scores, length or height-for-age z-scores, and weight-for-height z-scores. Nasopharyngeal aspirates (NPAs) were obtained and viral respiratory pathogens were identified using reverse transcription polymerase chain reactions (RT-PCR). Respiratory syncytial virus (RSV) load was assessed using quantitative RT-PCR. NPA and plasma leptin level were measured. Clinical data and nutritional status were recorded, and patients were followed up until hospital discharge. Viral coinfection was defined as the presence of two or more viruses detected in the same respiratory sample. Severity of illness was determined by length of hospitalization and duration of oxygen therapy. Results: Children with overnutrition showed a greater frequency of viral coinfection than those with normal weight (71% obese vs. 37% normal weight p = 0.013; 68% overweight vs. 37% normal weight p = 0.004). A lower RSV load was found in obese (5.91 log10 copies/mL) and overweight children (6.49 log10 copies/mL) compared to normal weight children (8.06 log10 copies/mL; p = 0.021 in both cases). In multivariate analysis, obese, and overweight infants <6 months old were associated with longer hospital stays (RR = 1.68; CI: 1.30-2.15 and obese: RR = 1.68; CI: 1.01-2.71, respectively) as well as a greater duration of oxygen therapy (RR = 1.80; IC: 1.41-2.29 and obese: RR = 1.91; CI: 1.15-3.15, respectively). Obese children <6 months showed higher plasma leptin level than normal weight children (7.58 vs. 5.12 ng/µl; p <0.046). Conclusions: In infants younger than 6 months, overnutrition condition was related to increased severity of infections and high plasma leptin level. Also, children with overnutrition showed a greater frequency of viral coinfection and low RSV viral load compared to normal weights children. These findings further contribute to the already existent evidence supporting the importance of overnutrition prevention in pediatric populations.

Chile's National Advisory Committee on Immunization (CAVEI): Evidence-based recommendations for public policy decision-making on vaccines and immunization.

A National Immunization Technical Advisory Group (NITAG) provides independent, evidence-based recommendations to the Ministry of Health for immunization programmes and policy formulation. In this article, we describe the structure, functioning and work processes of Chile's NITAG (CAVEI) and assess its functionality, quality of work processes and outputs, and integration of the committee into the Ministry of Health policy process using the Assessment tool for National Immunization Technical Advisory Groups. Among its strengths, CAVEI's administrative and work plasticity allows it to respond in a timely manner to the Ministry of Health's requests and proactively raise subjects for review. Representation of multiple areas of expertise within the committee makes CAVEI a robust and balanced entity for the development of evidence-based comprehensive recommendations. High ranking profile of the Secretariat structure furthers CAVEI's competences in policymaking and serves as a bridge between the committee and international initiatives in the field of immunizations.

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant.

Inherited IL-12Rß1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common TYK2 P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls (P = 8.37 × 10-8; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-α, IL-10, or even IL-12, which, like IL-23, induces IFN-γ via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of TYK2 selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis.

[Recurrent respiratory papillomatosis in a pediatric patient: case report]. / Papilomatosis respiratoria recurrente en paciente pediátrico: reporte de un caso.

Genetic variability related to the host immune system has been proposed as one of the most influential factors in the development of diseases caused by HPV. CLINICAL CASE: We report the case of a 5-year-old child in whom chronic laryngeal papillomatosis, probably acquired vertically during labor, was detected. The diagnosis of laryngeal papillomatosis was confirmed with a biopsy after a first surgery to remove the papillomas. The Derkay classification system was used to assess the severity of papillomatosis. Biopsy genotyping was performed by demonstrating HPV-6. Later, HLA-DQA1 * 0505, -DQB1 * 0301, -DRB1 * 1101 alleles were homozygous for HLA allele typing. CONCLUSIONS: Further studies are needed to identify the most prevalent HLA alleles in the Latino population and their potential association with genetic susceptibility in Recurrent Respiratory Papillomatosis.

Papilomatosis respiratoria recurrente en paciente pediátrico: reporte de un caso / Recurrent respiratory papillomatosis in a pediatric patient: case report

La variabilidad genética relacionada al sistema inmune del huésped ha sido propuesta como uno de los factores más influyentes en el desarrollo de enfermedades causadas por HPV. Caso clínico: Reportamos el caso de un niño de 5 años en cuyo estudio por disfonía crónica se encuentra papilomatosis laríngea probablemente adquirida por vía vertical durante el parto. El diagnóstico de papilomatosis laríngea se confirmó con una biopsia tras una primera cirugía orientada a remover los papilomas. Se utilizó el sistema de clasificación Derkay para evaluar la severidad de la papilomatosis. Se realizó genotipificación en biopsia demostrándose HPV-6. Posteriormente mediante tipificación de alelos HLA se demostró homocigosis para los alelos HLA-DQA1*0505, -DQB1*0301, -DRB1*1101. Conclusiones: Se necesitan estudios adicionales que permitan identificar los alelos HLA más prevalentes en población latina y su potencial asociación con la susceptibilidad genética en Papilomatosis Respiratoria Recurrente.

Genetic variability related to the host immune system has been proposed as one of the most influential factors in the development of diseases caused by HPV. Clinical case: We report the case of a 5-year-old child in whom chronic laryngeal papillomatosis, probably acquired vertically during labor, was detected. The diagnosis of laryngeal papillomatosis was confirmed with a biopsy after a first surgery to remove the papillomas. The Derkay classification system was used to assess the severity of papillomatosis. Biopsy genotyping was performed by demonstrating HPV-6. Later, HLA-DQA1 * 0505, -DQB1 * 0301, -DRB1 * 1101 alleles were homozygous for HLA allele typing. Conclusions: Further studies are needed to identify the most prevalent HLA alleles in the Latino population and their potential association with genetic susceptibility in Recurrent Respiratory Papillomatosis.

Deficiencia de anticuerpos específicos: inmunodeficiencia primaria asociada a alergia respiratoria / Specific antibody deficiency: primary immunodeficiency associated to respiratory allergy

La deficiencia de anticuerpos específicos con inmunoglobulinas séricas y linfocitos B normales (SAD) es una inmunodeficiencia primaria caracterizada por una capacidad alterada de responder a antígenos específicos, especialmente polisacáridos. OBJETIVO: Describir las características clínicas de pacientes con SAD y destacar la asociación entre una inmunodeficiencia primaria y enfermedades alérgicas. Pacientes y Método: Estudio descriptivo en enfermos con SAD atendidos en un hospital público entre agosto de 2007 y julio de 2015. Se descartó otra inmunodeficiencia primaria o secundaria. El diagnóstico se basó en infecciones recurrentes y una respuesta anormal a la vacuna neumocócica polisacárida con medición de IgG específica para 10 serotipos de neumococo. RESULTADOS: Se incluyeron 12 pacientes, 4 varones, con una edad promedio de 6 años; predominaron las neumonías recurrentes (91,7%) y otras infecciones respiratorias e invasivas. Los 12 enfermos con SAD tenían asma asociada; 11, rinitis alérgica y otras alergias. Tres pacientes no respondieron a ninguno de los 10 serotipos contenidos en la vacuna neumocócica polisacárida y la mayoría de los que lo hicieron fue a títulos bajos. El tratamiento con vacuna neumocócica conjugada fue favorable en 11/12 enfermos. CONCLUSIÓN: En niños mayores de 2 años con infecciones respiratorias recurrentes o infecciones invasivas por S. pneumoniae con inmunoglobulinas normales recomendamos investigar SAD, más aún si tienen enfermedad alérgica asociada.

Specific antibody deficiency (SAD) with normal immunoglobulin and normal B cells is a primary immunodeficiency characterized by reduced ability to produce antibodies to specific antigens especially polysaccharides. OBJECTIVE: To describe the characteristics of patients diagnosed with SAD emphasizing the association between primary immunodeficiency and allergic diseases. PATIENTS AND METHOD: Descriptive study showing patients with SAD treated at a public hospital between August 2007 and July 2015. Other secondary or primary immunodeficiency was discarded. The diagnosis of SAD was based on recurrent infections and abnormal response to pneumococcal polysaccharide vaccine assessed by specific IgG to 10 pneumococcal serotypes. Results: Twelve patients were included, 4 males, mean age 6 years, recurrent pneumonia predominated (91.7%) as well as other respiratory and invasive infections. All patients with SAD had associated asthma, 11 had allergic rhinitis, and other allergies. Three patients did not respond to any of the 10 serotypes contained in pneumococcal polysaccharide vaccine, and those who responded were with low titers. Treatment with conjugate pneumococcal vaccine was favorable in 11/12 patients. CONCLUSION: In children older than 2 years with recurrent respiratory infections or invasive S. pneumoniae infections with normal immunoglobulin we recommend to investigate SAD, especially if they have a concurrent allergic disease.

[Specific antibody deficiency: Primary immunodeficiency associated to respiratory allergy]. / Deficiencia de anticuerpos específicos: inmunodeficiencia primaria asociada a alergia respiratoria.

Specific antibody deficiency (SAD) with normal immunoglobulin and normal B cells is a primary immunodeficiency characterized by reduced ability to produce antibodies to specific antigens especially polysaccharides. OBJECTIVE: To describe the characteristics of patients diagnosed with SAD emphasizing the association between primary immunodeficiency and allergic diseases. PATIENTS AND METHOD: Descriptive study showing patients with SAD treated at a public hospital between August 2007 and July 2015. Other secondary or primary immunodeficiency was discarded. The diagnosis of SAD was based on recurrent infections and abnormal response to pneumococcal polysaccharide vaccine assessed by specific IgG to 10 pneumococcal serotypes. RESULTS: Twelve patients were included, 4 males, mean age 6 years, recurrent pneumonia predominated (91.7%) as well as other respiratory and invasive infections. All patients with SAD had associated asthma, 11 had allergic rhinitis, and other allergies. Three patients did not respond to any of the 10 serotypes contained in pneumococcal polysaccharide vaccine, and those who responded were with low titers. Treatment with conjugate pneumococcal vaccine was favorable in 11/12 patients. CONCLUSION: In children older than 2 years with recurrent respiratory infections or invasive S. pneumoniae infections with normal immunoglobulin we recommend to investigate SAD, especially if they have a concurrent allergic disease.