Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.

BACKGROUND: Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. METHODS: We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. RESULTS: During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. CONCLUSIONS: Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.

Impact of Acute High Glucose on Mitochondrial Function in a Model of Endothelial Cells: Role of PDGF-C.

An increase in plasma high glucose promotes endothelial dysfunction mainly through increasing mitochondrial ROS production. High glucose ROS-induced has been implicated in the fragmentation of the mitochondrial network, mainly by an unbalance expression of mitochondrial fusion and fission proteins. Mitochondrial dynamics alterations affect cellular bioenergetics. Here, we assessed the effect of PDGF-C on mitochondrial dynamics and glycolytic and mitochondrial metabolism in a model of endothelial dysfunction induced by high glucose. High glucose induced a fragmented mitochondrial phenotype associated with the reduced expression of OPA1 protein, high DRP1pSer616 levels and reduced basal respiration, maximal respiration, spare respiratory capacity, non-mitochondrial oxygen consumption and ATP production, regarding normal glucose. In these conditions, PDGF-C significantly increased the expression of OPA1 fusion protein, diminished DRP1pSer616 levels and restored the mitochondrial network. On mitochondrial function, PDGF-C increased the non-mitochondrial oxygen consumption diminished by high glucose conditions. These results suggest that PDGF-C modulates the damage induced by HG on the mitochondrial network and morphology of human aortic endothelial cells; additionally, it compensates for the alteration in the energetic phenotype induced by HG.

Effect of Platelet-Derived Growth Factor C on Mitochondrial Oxidative Stress Induced by High d-Glucose in Human Aortic Endothelial Cells.

Endothelial dysfunction is an early marker for cardiovascular diseases. Hyperglycemia induces endothelial dysfunction, increasing the production of reactive oxygen species. Platelet-derived growth factor C stimulates angiogenesis and revascularization in ischemic tissues of diabetic mice and promotes the migration of progenitors and mature ECs to injury sites; however, the molecular mechanisms of its actions are not described yet. Here, we evaluated the effect of PDGF-C on oxidative stress induced by HG. Human aortic endothelial cells were grown in glucose concentrations ranging from 5 mmol/L to 35 mmol/L for 1 to 24 h. Treatment with 50 ng/mL PDGF-C was done for 1 to 3 h. Cytosolic and mitochondrial ROS were measured by fluorometry, and the expression of antioxidant enzymes was evaluated by Western blot. Nrf2 and Keap1 expression was assessed by real-time PCR. High glucose induced mitochondrial ROS production. PDGF-C diminished the oxidative stress induced by high glucose, increasing SOD2 expression and SOD activity, and modulating the Keap1 expression gene. These results give new evidence about the mitochondrial antioxidant effect that PDGF-C could exert on endothelial cells exposed to high glucose and its considerable role as a therapeutic target in diabetes.

Clinical, laboratory and immune aspects of Zika virus-associated encephalitis in children.

OBJECTIVE: To evaluate the clinical, laboratory, and immune characteristics of Zika virus (ZIKV)-associated encephalitis in pediatric patients after the epidemic in Huila, southern Colombia. METHODS: A pediatric neuro-surveillance hospital study was conducted in a referral health center in southern Colombia, from October 2016 to October 2017. Cases of encephalitis were confirmed by nucleic acid amplification tests and serological methods in cerebrospinal fluid (CSF), plasma, and/or urine. Levels of six cytokines were evaluated by flow cytometry. Patients underwent daily clinical and laboratory follow-up. RESULTS: Twenty children with probable encephalitis were included for further studies and 16 of them were confirmed. Four cases of bacterial meningoencephalitis (Streptococcus pneumoniae, group B Streptococcus, Staphylococcus epidermidis, and Escherichia coli) and 12 cases of viral encephalitis were identified, six of them associated with ZIKV infection. Other viral encephalitis cases were caused by herpes viruses (n=3), enterovirus (n=2), and dengue virus type 2 (DENV-2; n=1) infections. ZIKV-associated encephalitis symptoms subsided faster than those of patients with encephalitis caused by other agents. CSF analysis revealed lymphocytic pleocytosis. Compared to healthy controls, children with ZIKV-associated encephalitis presented modest plasma interleukin (IL)-10 but not IL-2, IL-4, IL-6, interferon gamma (IFN-γ), or tumor necrosis factor alpha (TNF-α). Cytokine expression was differentially regulated, as dramatically elevated IL-6, IL-10, and IFN-γ levels were observed in CSF but not in paired plasma samples in one of the patients with ZIKV detectable in CSF. CONCLUSIONS: This study provides evidence that ZIKV is responsible for pediatric encephalitis in endemic areas, and the local presence of the virus may induce cephalic but not systemic expression of cytokines.

Procedimientos endoscópicos y pandemia COVID-19: consideraciones básicas / Basic considerations regarding endoscopic procedures during the COVID-19 pandemic

El SARS-Cov-2 es un coronavirus productor de la enfermedad COVID-19. Esta inició en Wuhan, capital de la provincia Hubei, China. En menos de cuatro meses la enfermedad se dispersó por el mundo, lo que dio origen a miles de muertes. La Organización Mundial de la Salud (OMS) la ha declarado pandemia. La humanidad está consternada, múltiples gobiernos han obligado al aislamiento total, con éxito variable debido a la negligencia de parte de la comunidad. En muchas ciudades las instituciones y el personal sanitario no son suficientes para atender la catástrofe. El aislamiento es la única estrategia eficaz para detener el crecimiento logarítmico de COVID-19. El motivo científico del aislamiento es que más del 60 % de los contagios surgen de personas asintomáticas. La enfermedad no solo produce síntomas respiratorios. El SARS-Cov-2, además, puede producir náuseas, dolor abdominal, vómito, diarrea, anosmia y ageusia. El 50% de los infectados pueden tener síntomas digestivos, que incluso preceden a los respiratorios. La ruta fecal-oral trasmite el virus, aún sin diarrea. En las unidades de endoscopia están todas las formas de contagio: aerosoles (vómitos, arcadas, eructos, flatos), materia fecal, contacto estrecho, contaminación del ambiente. Se deben suspender todas las endoscopias programadas para diagnóstico. Solo deben realizarse las urgentes y terapéuticas. Todo el personal de endoscopia debe tener medidas de protección estrictas. El paciente debe saber que en la sala de endoscopia puede contagiarse, con constancia en el consentimiento informado. Debe contactarse al paciente posendoscopia vía telefónica a los días 7 y 14 para indagar sobre todos los síntomas mencionados.(AU)

SARS-CoV-2 is the coronavirus which produces the dreaded COVID-19. Starting in Wuhan, the capital of China's Hubei province, it has spread it spread throughout the world in less than four months and has caused thousands of deaths. The WHO has declared it to be a pandemic. Humanity is shocked, and many governments have imposed total isolation. It has had varying success due to community negligence. In many cities, institutions and health personnel have not successfully managed this catastrophe. Isolation is the only effective strategy to stop the logarithmic growth of COVID 19. The scientific reason for isolation is that more than 60 % of infections arise from asymptomatic people. SARS-CoV-2 not only produces respiratory symptoms but can also cause nausea, abdominal pain, vomiting, diarrhea, anosmia and ageusia. Fifty percent of those infected may have digestive symptoms which may even precede respiratory symptoms. The fecal-oral route can transmit the virus even when there is no diarrhea. All forms of contagion are found in endoscopy units: aerosols from vomiting, retching, bel-ching, and flatus; fecal matter, close contact, and contamination of the environment. All diagnostic endoscopies should be discontinued. Only urgent and therapeutic endoscopy should be performed. All endoscopy personnel must have strict protection measures. Each patient should be informed, and sign an informed consent form, that the virus can be spread within the endoscopy room. After performance of endoscopy, the patient should be contacted by phone on days 7 and 14 to inquire about all symptoms mentioned.(AU)

Anticuerpos IgG4 específicos anti Aedes aegypti como factor protector en niños con dengue grave / Aedes aegypti-specifc IgG4 Antibodies as a Protection Factor in Children with Severe Dengue / Anticorpos IgG4 específicos anti-aedes aegypti como fator de proteção em crianças com dengue grave

Resumen: Introducción: La infección por el virus del dengue es un problema de salud pública mundial. El virus es transmitido por la picadura de mosquitos del género Aedes. Las proteínas de la saliva del vector Aedes aegypti inducen anticuerpos IgE e IgG4 específicos, cuya relación con la gravedad del dengue aún es desconocida. Objetivo: Evaluar la asociación entre anticuerpos IgE e IgG4 específicos anti A. aegypti con la gravedad de la infección por dengue. Método: Se realizó un estudio transversal en el que se incluyeron 16 niños con dengue grave (DG), 15 niños con dengue con signos de alarma (DCSA) y 26 niños sanos, todos menores de 15 años. Se determinaron niveles séricos de IgE e IgG4 específicas de A. aegypti; también se cuantificó VEGF, SST2 y VEGFRI por ELISA. Para las variables cualitativas se calcularon proporciones y odds ratio (OR); en las variables cuantitativas se hallaron medianas, rango intercuartílico y se utilizó la prueba U Mann Whitney. Resultados: La oportunidad de los niños de tener dg con niveles séricos de IgG4 específica mayores de 0,5 OD es 78 % menor [OR=0,22] (IC de 95 % de 0,06-0,77), comparado con la oportunidad de tener dg con niveles séricos de IgG4 específica menores de 0,5 OD. Plaquetas (p=0,0002) y VEFG (p=0,003) más elevado en los pacientes con DCSA y SST2 fue más alto en el DG (p=0,004). Conclusión: Niveles de anticuerpos de IgG4 anti A. aegypti se relacionan con menor gravedad clínica del dengue.

Abstract: Introduction: Dengue virus infection is a global public health problem. The bite of Aedes mosquitoes transmits the virus. The proteins in the saliva of the Aedes aegypti vector induce specific IgE and IgG4 antibodies, whose relationship with the severity of dengue is still unknown. Aim: To evaluate the association between A. aegypti-specific IgE and IgG4 antibodies and the severity of dengue infection. Method: A cross-sectional study was carried out involving 16 children with severe dengue (DG), 15 children with dengue and warning signs (DCSA), and 26 healthy children, all of them under 15 years of age. Serum levels of A. aegypti-specific IgE and IgG4 were determined; VEGF, SST2, and VEGFRI were also quantified by ELISA. For the qualitative variables, proportions and odds ratios (OR) were calculated; as to the quantitative variables, medians and interquartile range were found and the U Mann Whitney test was used. Results: Children's chance of having DG with specific IgG4 serum levels greater than 0.5 DO is 78 % lower [OR = 0.22] (95% CI, 0.06-0.77), compared to the possibility of having dg with specific IgG4 serum levels less than 0.5 DO. Platelets (p = 0.0002) and VEFG (p = 0.003) that are higher in patients with DCSA and SST2 were higher in DG (p = 0.004). Conclusion: A. aegypti-specific IgG4 antibody levels are related to lower clinical severity of dengue.

Resumo: Introdução: A infecção pelo vírus da dengue é um problema mundial de saúde pública. O vírus é transmitido pela picada de mosquitos do gênero Aedes. As proteínas na saliva do vetor Aedes aegypti induzem anticorpos IgE e IgG4 específicos, cuja relação com a gravidade da dengue ainda é desconhecida. Objetivo: Avaliar a associação entre anticorpos IgE e IgG4 específicos Anti-Aedes ae-gypti com a gravidade da infecção por dengue. Método: Foi realizado um estudo transversal no qual foram incluídas 16 crianças com dengue grave (DG), 15 crianças com dengue com sinais de alarme (DCSA) e 26 crianças saudáveis, todas com menos de 15 anos de idade. Os níveis séricos de IgE e IgG4 específicos para Aedes aegypti foram determinados. VEGF, SST2 e VEGFR1 também foram quantificados por ELISA. Para as variáveis qualitativas, foram calculadas proporções e odds ratio (OR). Nas variáveis quantitativas foram encontradas medianas, intervalo interquartil e utilizado o teste U de Mann Whitney. Resultados: A chance de as crianças terem dg com níveis séricos de IgG4 específica maiores que 0,5 od é 78% menor [OR=0,22] (IC 95% 0,06-0,77), em comparação com a chance delas terem dg com níveis séricos de IgG4 específica menor que 0,5 od. As plaquetas (p=0,0002) e VEFG (p=0,003) foram maiores nos pacientes com DCSA e o SST2 foi maior no DG (p=0,004). Conclusão: Os níveis de anticorpos IgG4 Anti-Aedes aegypti estão relacionados à menor gravidade clínica da dengue.

Inmunodeficiencia combinada severa (SCID) en Neiva, Colombia. Reporte de caso / Severe combined immunodeficiency (SCID) in Neiva, Colombia: Case Report

Resumen Introducción. Las inmunodeficiencias primarias son enfermedades genéticas del sistema inmune que incrementan la susceptibilidad a infecciones. Una de las formas más graves en niños es la inmunodeficiencia combinada severa. Presentación del caso. Se presenta el caso de un niño que fue diagnosticado con inmunodeficiencia combinada severa; este era un paciente masculino de ocho meses que presentó cuadro clínico consistente en múltiples hospitalizaciones debido a infección por citomegalovirus, endocarditis por Candida albicans e infección recurrente de las vías urinarias por Pseudomonas aeruginosa. El perfil inmunológico mostró disminución del número absoluto de células CD3+ y CD19+, lo que permitió realizar el diagnóstico de inmunodeficiencia combinada severa instaurándose manejo; sin embargo, el niño no se recuperó y falleció. Conclusiones. Las inmunodeficiencias primarias son patologías que requieren una intervención oportuna que permita brindar un mejor pronóstico a los pacientes.

Abstract Introduction: Primary immunodeficiencies are genetic disorders of the immune system that increase susceptibility to infections. One of the most serious forms in children is severe combined immunodeficiency. Case presentation: This is the report of the case of an 8-monthold male patient who was diagnosed with severe combined immunodeficiency. The child presented a clinical profile consisting of multiple hospitalizations due to cytomegalovirus infection, endocarditis by Candida albicans and recurrent urinary tract infection by Pseudomonas aeruginosa. The immune profile showed a decrease in the absolute number of CD3+ and CD19+ cells, which led to the diagnosis of severe combined immunodeficiency. Even though management was established, the child did not recover and died. Conclusions: The primary immunodeficiencies are disorders that require timely intervention to provide a better prognosis to patients.

[Urban outbreak of leishmaniasis in Colombia]. / Brote urbano de leishmaniasis en Colombia.

OBJECTIVES: To describe the epidemiology, clinical characteristics and treatment of children with visceral Leishmaniasis in Neiva- Huila, from April to June 2012. METHODOLOGY: We performed a descriptive study of an outbreak of visceral leshmaniasis in children from the urban area of Neiva. RESULTS: There were seven cases in children younger than five years. All of them had prolonged fever, hepato-splenomegaly, severe anemia and leukopenia. Five were admitted with severe thrombocytopenia, without hemorrhagic manifestations. Six patients received first-line treatment with miltefosine, five of them had treatment failure requirirng therapy escalation to amphotericin B, two received liposomal amphotericin B and three deoxycholate amphotericin B. The main vector identified was the Lutzomyia gomezi and its main reservoir were canines. CONCLUSION: We describe the first visceral leishmaniasis outbreak in children living in an urban area, with no mortality. Most of the cases had a good response to amphotericin B.

OBJETIVOS: Describir las características epidemiológicas, clínicas y el tratamiento de niños con leishmaniasis visceral en Neiva, Huila. METODOLOGIA: Se realizó un estudio descriptivo del brote de leshmaniasis visceral en niños de la zona urbana de Neiva, Huila, entre los meses de abril a junio de 2012. RESULTADOS: Se presentaron siete casos, en niños menores de cinco años, con fiebre prolongada, hepato-esplenomegalia, anemia severa y leucopenia. Cinco ingresaron con trombocitopenia severa, sin manifestaciones hemorrágicas. Seis pacientes recibieron manejo de primera línea con miltefosine, cinco presentaron fracaso terapéutico y se escalonó tratamiento a anfotericina B, de los cuales dos recibieron anfotericina liposomal y tres anfotericina deoxicolato. El principal vector identificado fue la Lutzomyia gomezi y los reservoirios indentifiacados fueron caninos. CONCLUSIÓN: Se describe el primer brote de leishmaniasis visceral en zona urbana, en población pediátrica sin casos de mortalidad. La mayoría de los casos con buena respuesta a Anfotericina B.

Extracts of Physalis peruviana Protect Astrocytic Cells Under Oxidative Stress With Rotenone.

The use of medicinal plants to counteract the oxidative damage in neurodegenerative diseases has steadily increased over the last few years. However, the rationale for using these natural compounds and their therapeutic benefit are not well explored. In this study, we evaluated the effect of different Physalis peruviana extracts on astrocytic cells (T98G) subjected to oxidative damage induced by rotenone. Extracts of fresh and dehydrated fruits of the plant with different polarities were prepared and tested in vitro. Our results demonstrated that the ethanolic extract of fresh fruits (EF) and acetone-dehydrated fruit extract (AD) increased cell viability, reduced the formation of reactive oxygen species (ROS) and preserved mitochondrial membrane potential. In contrast, we observed a significant reduction in mitochondrial mass when rotenone-treated cells were co-treated with EF and AD. These effects were accompanied by a reduction in the percentage of cells with fragmented/condensed nuclei and increased expression of endogenous antioxidant defense survival proteins such as ERK1/2. In conclusion, our findings suggest that ethanolic and acetone extracts from P. peruviana are potential medicinal plant extracts to overcome oxidative damage induced by neurotoxic compounds.

First Analysis of SERPING1 Gene in Patients with Hereditary Angioedema in Colombia Reveals Two Genotypic Variants in a Highly Symptomatic Individual.

Hereditary angioedema (HAE) is a heterogeneous genetic disease caused by a deficit in C1 inhibitor (C1-INH) and clinically characterized by sudden events of edema, swelling, and pruritus. Here, we describe the first SERPING1 genotyping in 22 subjects from 4 non-related families, all from southern Colombia. The previously reported heterozygous gene mutations, c.1081C>T (p.Gln361*), c.1396C>G (p.Arg466Gly), c.1029+84G>A, or c.106_107del (p.Ser36Phefs*21), were found in 12 patients. Of note, a single patient clinically characterized as severe HAE type 2 expressed mutations in exon 8 and intron 6, whereas all the others have type 1 HAE and expressed one pathogenic variant. One of the subjects, a 5-year-old girl was discovered to have a pathogenic variant, and she is still asymptomatic. This is the first report focused on HAE genetic analysis in a Colombian population.

Brote urbano de leishmaniasis en Colombia / Urban outbreak of leishmaniasis in Colombia

RESUMEN Objetivos Describir las características epidemiológicas, clínicas y el tratamiento de niños con leishmaniasis visceral en Neiva, Huila. Metodologia Se realizó un estudio descriptivo del brote de leshmaniasis visceral en niños de la zona urbana de Neiva, Huila, entre los meses de abril a junio de 2012. Resultados Se presentaron siete casos, en niños menores de cinco años, con fiebre prolongada, hepato-esplenomegalia, anemia severa y leucopenia. Cinco ingresaron con trombocitopenia severa, sin manifestaciones hemorrágicas. Seis pacientes recibieron manejo de primera línea con miltefosine, cinco presentaron fracaso terapéutico y se escalonó tratamiento a anfotericina B, de los cuales dos recibieron anfotericina liposomal y tres anfotericina deoxicolato. El principal vector identificado fue la Lutzomyia gomezi y los reservoirios indentifiacados fueron caninos. Conclusión Se describe el primer brote de leishmaniasis visceral en zona urbana, en población pediátrica sin casos de mortalidad. La mayoría de los casos con buena respuesta a Anfotericina B.(AU)

ABSTRACT Objectives To describe the epidemiology, clinical characteristics and treatment of children with visceral Leishmaniasis in Neiva- Huila, from April to June 2012. Methodology We performed a descriptive study of an outbreak of visceral leshmaniasis in children from the urban area of Neiva. Results There were seven cases in children younger than five years. All of them had prolonged fever, hepato-splenomegaly, severe anemia and leukopenia. Five were admitted with severe thrombocytopenia, without hemorrhagic manifestations. Six patients received first-line treatment with miltefosine, five of them had treatment failure requirirng therapy escalation to amphotericin B, two received liposomal amphotericin B and three deoxycholate amphotericin B. The main vector identified was the Lutzomyia gomezi and its main reservoir were canines. Conclusion We describe the first visceral leishmaniasis outbreak in children living in an urban area, with no mortality. Most of the cases had a good response to amphotericin B.(AU)

Análisis descriptivo del compromiso de órganos en niños con dengue grave en Neiva, Colombia / Descriptive analysis of organ involvement in children with severe dengue in Neiva, Colombia

Resumen Introducción. La infección por dengue puede comprometer órganos como el miocardio y el hígado. Tal hecho puede agravar la evolución clínica, por ello estos órganos han sido considerados en la clasificación revisada de la Organización Mundial de la Salud (OMS) para esta enfermedad. Objetivo. Describir la presencia de afectación por dengue en órganos como miocardio, hígado y sistema nervioso central (SNC) en niños de Neiva, Colombia Materiales y métodos. Este estudio analizó 930 niños con diagnóstico de dengue confirmado que ingresaron al Hospital Universitario Hernando Moncaleano Perdomo de Neiva entre enero de 2009 y diciembre de 2010. Para el diagnóstico y estratificación clínica se usó la clasificación revisada de la OMS. La infección por dengue se confirmó por detección plasmática de NS1 o IgM específica. Se realizó seguimiento clínico y paraclínico diario durante toda la hospitalización. Resultados. De los 930 niños, 105 fueron clasificados como dengue grave (DG) y, de estos, 19 presentaron órganos afectados. El miocardio fue el más comprometido (14 casos), seguido por el hígado (4 casos) y el SNC (1 caso). Conclusión. El compromiso clínico del miocardio, el hígado o el SNC se observó en el 18% de los casos de niños con DG. Es necesario un diagnóstico y tratamiento oportuno de esta patología en niños.

Abstract Introduction: Dengue can compromise organs such as the myocardium and the liver. Clinical evolution may be aggravated by this fact, and for that reason, these organs have been considered in the revised classification of the World Health Organization (WHO) for this disease. Objective: To describe the affectation caused by dengue in organs such as the myocardium, the liver and the central nervous system (CNS) in children from Neiva, Colombia. Materials and methods: This study analyzed 930 children diagnosed with confirmed dengue and admitted to the Hernando Moncaleano Perdomo University Hospital of Neiva between January 2009 and December 2010. Diagnosis and clinical stratification were obtained based on the revised WHO classification. Dengue infection was confirmed by NS1 or specific IgM plasma detection. Daily clinical and paraclinical follow-up was performed during the full length of hospital stay. Results: Out of 930 children, 105 were classified as severe dengue (SD) and, of these, 19 had affected organs. The myocardium was the most compromised organ (14 cases), followed by the liver (4 cases) and the CNS (1 case). Conclusion: Clinical involvement of the myocardium, liver or CNS was observed in 18% of the cases of children with SD. A timely diagnosis and treatment of this pathology in children is necessary.

Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections.

The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6-12 months old) and children (1-14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = -0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue.

Altered immune parameters correlate with infection-related hospitalizations in children with Down syndrome.

In addition to previously studied immunological variables, the relative expression of IFNGR2, IFNAR1, CD18, and CD275 (all encoded in chromosome 21) on circulating leucocytes and multifunctional T cells (evaluated by an intracellular cytokine/proliferation assay) were compared between children with Down syndrome (DS) and healthy controls (HC). As previously reported, numbers of lymphocytes, CD4(+) T cells, Treg cells, B cells, and levels of serum IgM were decreased, and levels of IgG and IgA were increased in children with DS. Moreover, the relative expression of CD18 on T and B cells (previously and not previously reported, respectively) were elevated in DS children (p⩽0.01). Age and numbers of B and Treg cells moderately correlated with retrospectively identified infection related hospitalizations (rho: 0.300-0.460, p⩽0.003). Age and the numbers of Treg cells also correlated with prospectively identified infection related hospitalizations. Future studies are necessary to clarify the role of these parameters in the immunity of DS patients.

Estudio de brote de enfermedad transmitida por alimentos / Study for outbreak desease transmitted through food / Estudo para transmitir surto de doença alimentos

Objetivo: Caracterizar el brote de enfermedad transmitida por alimentos ocurrido en un batallón militar y en algunos jardines infantiles en la ciudad de Bogotá en Julio de 2013. Materiales y Métodos: Estudio analítico de Cohortes, con una población de 100 militares y una muestra de 50 individuos a quienes se aplicó entrevista de consumidores. Por una posible conexión, se realizó evaluación de factores de riesgo en 15 hogares infantiles de los cuales se obtuvo una muestra de 52 manipuladores de alimentos a través de encuesta como segundo instrumento de Inspección, Vigilancia y Control y muestreos microbiológicos de superficies y manipuladores. Resultados: Se encontró una tasa de ataque para la mayonesa de 89%, RR de 7,9 y un intervalo de confianza de 3,4- 18,4. Para ninguno de los otros alimentos se evidenció significancia estadística. Conclusiones: De acuerdo a los resultados observados se concluye que la mayonesa es el posible factor causante de la enfermedad transmitida por alimentos. No se pudo determinar el agente causal, por las características de ejercicio.

Goal: To characterize outbreaks of foodborne illness occurred in a battalion and in some kindergartens in Bogota city in July 2013. Materials and Methods: Cohort analytic study, with a population of 100 army soldiersand a sample of 50 individuals were interviewed consumers was applied. According to a possible connection, an evaluation of the risk factors was performed in 15 children's homes which a sample of 52 food handlers was obtained through a survey as a second instrument Inspection, Monitoring and Control of microbiological sampling surfaces and handlers. Results: The rate of attack was found for mayonnaise 89%, RR 7.9 and a confidence interval of 3.4 to 18.4. For none of the other food showed statistical significance. Conclusions: According to the results observed it is concluded that mayonnaise is the possible causative factor of the disease cause by food. It was not possible to determine the causal agent because of the exercise´s characteristics.

Objetivo: Caracterizar os surtos de doenças transmitidas por alimentos ocorreu em um militar e,em alguns jardins de infância na cidade de Bogotá em julho de 2013 do batalhão. Materiais e Métodos: estudo de coorte analítica, com uma população de 100 militares e uma amostra de 50 indivíduos para entrevistar consumidores foi aplicado. Por conexão possível, a avaliação de fatores de risco foi realizada em 15 casas das crianças que uma amostra de 52 manipuladores de alimentos foram obtidos através de levantamento e segundo instrumento de Inspeção, Monitoramento e Controle de amostragem microbiológica superfícies e manipuladores. Resultados: A taxa de ataque foi encontrado para maionese 89%, RR 7.9 e um intervalo de confiança de 3,4-18,4. Para nenhum dos outros alimentos mostraram significância estatística. Conclusões: De acordo com os resultados Observou conclui-se que a maionese é o possível factor causal da doença transmitidas por alimentos. Não foi possível determinar o agente causal, a natureza da exercício.

Biomarcadores pronósticos de gravedad del dengue / Biomarkers for the prognosis of severe dengue

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Introduction: There are very few strategies for the early detection of the patients who might develop the severe form of the illness. Objective: To evaluate the utility of serum levels of some immune response mediators as early biomarkers for the severe dengue prognosis during the early phase of the illness. Materials and methods: Using a case-control design nested in a multicenter cohort from the AEDES network (a Colombian multicenter study), we compared TNF a, ST2, TRAIL and IDO levels in samples which were obtained during the early phase of the illness. Results: ST2, TRAIL and TNF a levels were higher in severe dengue patients compared with uncomplicated patients (p<0.0001), as follows: OR=24.8, CI95%= 6.1- 98.0; OR=18.0, CI95%= 4.6-69.1; OR=NC, CI95%= NC, respectively. We did not find statistically significant differences between IDO levels in severe dengue and uncomplicated dengue (p=1.000, OR=1.0, CI95%= 0.2-6.1). Conclusions: In the early phase of the dengue infection (96 hours), ST2, TRAIL and TNF a quantifications could contribute to the prediction of complications of the illness.

Dengue perinatal / Perinatal dengue

El dengue es en la actualidad la enfermedad viral más relevante de transmisión vectorial hiperendémica en las Américas. El incremento en el número de casos se ha relacionado con la aparición de dengue durante la gestación y en el periodo neonatal. De acuerdo con la edad de gestación en la que ocurra la infección, podrían presentarse manifestaciones en el feto, como aborto, y en los pacientes a término, dengue neonatal. En este artículo se presenta una reseña de los casos reportados a nivel mundial, y especialmente en las Américas, así como aspectos fisiopatogénicos de la enfermedad.

Dengue is currently the most important viral disease transmitted by arthropods and which is hyperendemic in the Americas. An increase in the number of cases is related to dengue during pregnancy and the neonatal period. According to the gestational age in which infection occurs, there could be different manifestations in the fetus including abortion, malformations or neonatal dengue in newborns. This article presents a review regarding some cases reported worldwide, especially in the Americas, and some pathophysiologic issues related to perinatal dengue.

High plasma levels of soluble ST2 but not its ligand IL-33 is associated with severe forms of pediatric dengue.

Identification of early determinants of dengue disease progression, which could potentially enable individualized patient care are needed at present times. Soluble ST2 (sST2) has been recently reported to be elevated in the serum of children older than 2 years old and adults with dengue infection and it was correlated with secondary infections as well as with severe presentations of the disease. The mechanism by which secreted ST2 is linked to severe dengue and plasma leakage remains unclear. One possibility is that IL-33 ligand may be elevated, contributing to membrane bound ST2 as part of the immune activation in dengue infection. We determined plasma levels of sST2 and the ligand IL-33 in 66 children with acute secondary dengue infections clinically classified using the guidelines of the World Health Organization, 2009. Dengue infection showed significant increases in cytokines IL-12p70, IL-10, IL-8, IL-6, IL-1ß and TNFα measured by flow cytometry based assay compared to uninfected individuals. In contrast, IL-33 levels remained unchanged between infected and uninfected individuals. The levels of sST2 positively correlated with values of IL-6 and IL-8 and inversely correlated with number of median value of platelet levels. In addition to circulating cytokine positive correlations we found that sST2 and isoenzyme creatine kinase-MB (CK-MB), a marker of myocardial muscle damage present in severe dengue cases were associated. Our pediatric study concluded that in dengue infections sST2 elevation does not involve concomitant changes of IL-33 ligand. We propose a study to assess its value as a predictor factor of disease severity.

[Perinatal dengue]. / Dengue perinatal.

Dengue is currently the most important viral disease transmitted by arthropods and which is hyperendemic in the Americas. An increase in the number of cases is related to dengue during pregnancy and the neonatal period. According to the gestational age in which infection occurs, there could be different manifestations in the fetus including abortion, malformations or neonatal dengue in newborns. This article presents a review regarding some cases reported worldwide, especially in the Americas, and some pathophysiologic issues related to perinatal dengue.