Macronutrients during pregnancy and life-threatening respiratory syncytial virus infections in children.

RATIONALE: Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. OBJECTIVES: We defined the burden of life-threatening (O(2) saturation [O(2) sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children's pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. METHODS: Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O(2) sat less than 93% on admission were included. MEASUREMENTS AND MAIN RESULTS: Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5-2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV(+)), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4-1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15-9.44] to 7.36 [95% CI, 2.41-22.5] versus the lowest quartile). CONCLUSIONS: Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.

Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina.

BACKGROUND: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. METHODS: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. RESULTS: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). CONCLUSIONS: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years.

A mechanistic role for type III IFN-λ1 in asthma exacerbations mediated by human rhinoviruses.

RATIONALE: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear. OBJECTIVES: To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing. METHODS: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma. MEASUREMENTS AND MAIN RESULTS: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21-2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-λ(1) levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-λ(1), children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57-2.46; P = 0.66). CONCLUSIONS: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-λ(1) responses mediate exacerbations caused by HRV. Modulation of IFN- λ(1) should be studied as a therapeutic target for exacerbations caused by HRV.

T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children.

BACKGROUND: The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, >90% of the population was DENV-naïve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection. METHODS: We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers. Lymphocyte T helper (Th) 1, Th2, Th17 and inflammatory responses were assayed in blood during the 2009 DENV-1 epidemic. RESULTS: The immune response to DENV-1 was significantly biased to Th2 in infected infants and young children, compared to infants with other febrile illnesses (for IL-4 p < 0.001) and to their infected mothers (for IL-4 p < 0.01). In addition, IL-17 suppression was observed in the memory response to DENV-1 in infected infants (p < 0.01 vs placebo). CONCLUSION: Age-related differences in the primary response to DENV, characterized by an immature Th2 polarization and Th17 suppression in infants, should be studied further in order to expand our understanding of the mechanism of dengue pathogenesis.

Cannabinoides y epilepsia / Cannabinoids and epilepsy

El uso de CBD en formulaciones estandarizadas y controladas (obviamente, esto excluye a las preparaciones caseras), en una concentración del 99% y nunca menor al 96% con respecto al THC, como tratamiento adyuvante en la epilepsia refractaria o fármacorresistente en niños y jóvenes, ha demostrado tener efecto anticonvulsivante principalmente en crisis motoras y debe considerarse como una opción efectiva y segura en el tratamiento de este tipo de pacientes. Más allá de su probada eficacia anticonvulsivante, permite en la mayoría de los casos reducir la dosis de otros fármacos anticonvulsivantes y sus efectos adversos, lo que resulta en mejoría de la calidad de vida de los pacientes y de sus cuidadores. El uso medicinal de los cannabinoides y sus compuestos no adictivos deben ser considerados dentro del arsenal terapéutico de uso controlado, en el tratamiento de la epilepsia refractaria.

Human rhinoviruses in severe respiratory disease in very low birth weight infants.

OBJECTIVES: To assess incidence, burden of illness, and risk factors for human rhinoviruses (HRVs) in a cohort of very low birth weight (VLBW) infants. METHODS: A 2-year prospective cohort study was conducted among VLBW premature infants in Buenos Aires, Argentina. Infants were enrolled in the NICU from June 1, 2003, to May 31, 2005, and managed monthly and with every acute respiratory illness (ARI) during the first year of life. Nasal wash samples were obtained during every respiratory episode and tested for HRV, respiratory syncytial virus (RSV), human parainfluenza viruses, influenza viruses, and human metapneumovirus using reverse transcriptase-polymerase chain reaction. RESULTS: Of 119 patients, 66 (55%) had HRV-associated ARIs. The incidence of HRV-associated ARI was 123 events per 100 child-years of follow-up. Of those infants experiencing an episode of bronchiolitis, 40% had HRV versus 7% with RSV. The incidence of HRV-associated bronchiolitis was 75 per 100 infant-years of follow-up. HRV was associated with 12 of 36 hospitalizations (33%), and RSV was associated with 9 of 36 hospitalizations (25%). The incidence of HRV-associated hospitalization was 12 per 100 infant-years of follow-up. The risk of HRV-associated hospitalization was higher for infants with bronchopulmonary dysplasia and those who were not breastfed. CONCLUSIONS: HRV is an important and frequent pathogen associated with severe respiratory infections in VLBW infants. Bronchopulmonary dysplasia and the absence of breastfeeding are risk factors for hospitalization. The results of our study reveal that HRV is the predominant pathogen of respiratory infections in premature infants.

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.

Does low birth weight predict obesity/overweight and metabolic syndrome in elementary school children?

BACKGROUND: We undertook this study to explore the relationship between birth weight (BW) and childhood overweight and obesity (OW/OB) and metabolic syndrome (MS). METHODS: This was a cross-sectional assessment performed in 10 elementary public schools in Buenos Aires, Argentina. Participants were 1027 students aged 9.4 +/- 2.1 years. No interventions were done. We measured the association between BW in children and OW/OB and MS at 9 years of age. RESULTS: Of the total number of children, 164 (16.0%) were OB (BMI >95(th) percentile) and 169 (16.5%) were OW [(body mass index (BMI) > or =85(th), <95(th) percentile); 61% were at Tanner 1. All students came from low socioeconomic families. The prevalence of low (< or =2500 g), normal, and high BW (> or =4000 g) was 7.0% (n = 72), 83.7% (n = 860), and 9.3% (n = 95), respectively. MS prevalence was 5.5%. There was a significant difference in mean BMI sd score (SDS) between low BW (0.07), normal BW (0.54) and high BW (0.99). There was a significant difference in mean BMI, BMI SDS, waist circumference (WC), WC SDS, and systolic blood pressure between low, normal, and high BW groups. In separate logistic regression models, low BW proved to be a protective factor against OW/OB [OR 0.32 (95% CI 0.16-0.63)], whereas high BW was associated with a higher OW/OB risk adjusted for age and sex [OR 2.48 (95% CI 1.62-3.81)]. The risk of MS was high for those with high BW [OR 3.16 (95% CI 1.38-7.24)] and not significant for those with low BW adjusted for age and sex. CONCLUSIONS: Our data indicate that low BW is not associated with OW/OB or with MS in children, whereas high BW correlates with childhood OW/OB and MS.