Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

Rapport de synthèse: Enjeux de la recherche : La pneumonie communautaire chez l'enfant est un problème de santé publique considérable. Elle est responsable de 2 millions de mort par année, 70% survenant dans les pays en voie de développement. Sous nos latitudes son incidence est de 40/1000 enfants par année, ce qui représente une morbidité importante. Deux difficultés surviennent lorsqu'on cherche à diagnostiquer une pneumonie. La première est de distinguer une pneumonie bactérienne d'une virale, particulièrement chez les petits enfants où les infections virales des voies respiratoires inférieures sont fréquentes. L'OMS a définit la pneumonie selon des critères exclusivement cliniques et une étude effectuée à Lausanne en 2000 a montré que ces critères peuvent être utilisés dans nos contrées. La seconde difficulté est de définir l'agent causal de la pneumonie, ceci pour plusieurs raisons : L'aspiration endotrachéale, seul examen fiable, ne peut être obtenue de routine chez l'enfant vu son caractère invasif, la culture des secrétions nasopharyngées reflète la flore physiologique de la sphère ORL et une bactériémie n'est présente que dans moins de 10% des pneumonies. L'étiologie de la pneumonie reste souvent inconnue, et de ce fait plusieurs enfants reçoivent des antibiotiques pour une infection non bactérienne ce qui contribue au développement de résistances. L'objectif de cette étude était d'effectuer une recherche extensive de l'agent causal de la pneumonie et de déterminer quels facteurs pourraient aider le clinicien à différencier une pneumonie virale de bactérienne, en corrélant l'étiologie avec la sévérité clinique et les marqueurs de l'inflammation. Contexte de la recherche : II s'agissait d'une étude prospective, multicentrique, incluant les enfants âgés de 2 mois à 5 ans hospitalisés pour une pneumonie, selon les critères de l'OMS, dans le service de pédiatrie de Lausanne et Genève entre mars 2003 et Décembre 2005, avant l'implantation de la vaccination antipneumococcique de routine. Chaque enfant, en plus des examens usuels, bénéficiait d'une recherche étiologique extensive : Culture virale et bactérienne, PCR (Mycoplasma Pneumoniae, Chlamydia Pneumoniae, Virus Influenza A et B, RSV A et B, Rhinovirus, Parainfluenza 1-3, enterovirus, human metapneumovirus, coronavirus OC43, E229 ; et NL 63) et détection d'AG viraux dans les sécrétions nasopharyngées ; sérologies virales et bactériennes à l'entrée et 3 semaines après la sortie (AG Influenza A et B, Parainfluenza 1,2 et 3, RSV, Adenovirus, M.Pneumoniae et S.Pneumoniae). Conclusions : Un agent pathogène a été découvert chez 86% des 99 patients retenus confirmant le fait que plus la recherche étiologique est étendue plus le pourcentage d'agent causal trouvé est élevé. Une infection bactérienne a été découverte chez 53% des patients dont 45% avaient une infection à S. Pneumoniae confirmant l'importance d'une vaccination antipneumococcique de routine. La déshydratation et les marqueurs de l'inflammation tels que la C-Reactive Protein et la Procalcitonine étaient significativement plus élevés dans les pneumonies bactériennes. Aucune corrélation n'a été trouvée entre le degré de sévérité de la pneumonie et l'étiologie. L'étude a confirmé la haute prévalence d'infections virales (67%) et de co-infection (33%) dans la pneumonie de l'enfant sans que l'on connaisse le rôle réel du virus dans la pathogenèse de la pneumonie. Perspectives : d'autres études à la suite de celle-ci devraient être effectuées en incluant les patients ambulatoires afin de déterminer, avec un collectif plus large de patient, une éventuelle corrélation entre sévérité clinique et étiologie. Abstract : Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization

Development of bioassays using the zebrafish larva model to screen endocrine disruptors for their involvement in the pathological progression of non-alcoholic fatty liver diseases

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CD40L-expressing CD4+ T cells prime adipose-derived stromal cells to produce inflammatory chemokines

International audienceThe therapeutic potential of culture-adapted adipose-derived stromal cells (ASCs) is largely related to their production of immunosuppressive factors that are inducible in vitro by priming with inflammatory stimuli, in particular tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). In vivo, obesity is associated with chronic inflammation of white adipose tissue, including accumulation of neutrophils, infiltration by IFNγ/TNFα-producing immune cells, and ASC dysfunction. In the current study, we identified in obese patients a simultaneous upregulation of CD40Lin the adipose tissue stroma vascular fraction (AT-SVF), correlated with the Th1 gene signature, and an overexpression of CD40 by native ASCs. Moreover, activated CD4+ T cells upregulated CD40 on culture-expanded ASCs and triggered their production of IL-8 in a CD40L-dependent manner, leading to an increased capacity to recruit neutrophils. Finally, activation of ASCs by sCD40L or CD40L-expressing CD4+ T cells relies on both canonical and non-canonical NF-κB pathways, and IL-8 was found to be coregulated with NF-κB family members in AT-SVF. These data identify the CD40-CD40L axis as a priming mechanism of ASCs, able to modulate their cross talk with neutrophils in an inflammatory context, and their functional capacity for therapeutic applications

Prevalence and associated factors for Chlamydia trachomatis infection among undocumented immigrants in a primary care facility in Geneva, Switzerland: a cross-sectional study

Chlamydia trachomatis infection (CTI) is the most frequent sexually transmitted infection in western countries. Its prevalence in undocumented immigrants, a rapidly growing vulnerable population, remains unknown. We aimed to document the prevalence of CTI and associated factors at the primary health care level. This cross-sectional study included all undocumented immigrants attending a health care facility in Geneva, Switzerland. Participants completed a questionnaire and were tested for CTI by PCR assay. Three-hundred thirteen undocumented immigrants (68.4% female, mean age 32.4 (SD 8) years) agreed to participate. CTI prevalence was 5.8% (95% CI 3.3-8.4). Factors associated with higher prevalence were age </=25 (OR 3.9, 95% CI 1.3-12.2) and having had two or more sexual partners during the precedent year (OR 4.5, 95% CI 1.5-13.7). Prevalence and associated factors for infection in this vulnerable population were comparable with other populations in Western countries. Our findings support the importance of facilitating access to existing screening opportunities in particular to individuals at higher risk

Lower respiratory viral illnesses: improved diagnosis by molecular methods and clinical impact

We assessed the frequency and the potential role of respiratory viruses on disease outcomes in hospitalized patients and lung transplant recipients who underwent a bronchoalveolar lavage (BAL) for an acute respiratory infection. BAL specimens (148) were analyzed by reverse transcription-polymerase chain reaction for the presence of 11 different viruses, as well as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Respiratory viruses were identified in 34 of 117 BAL specimens (29%) obtained in patients with a suspected respiratory infection and in only 2 of 31 control subjects (7%) (p < 0.01). M. pneumoniae was identified in five additional cases. Only 30% of cases that were virus positive by molecular methods were also positive by cell culture analysis. Rhinovirus was the most frequently identified virus (56% of cases) followed by respiratory syncytial virus (27%). In lung transplant recipients, the rate of viral infections was 55% in cases with respiratory symptoms compared with only 4% in control subjects (p < 0.001). In these cases, respiratory viral infections were associated with significant lung function abnormalities. By using reverse transcription-polymerase chain reaction assays, we frequently identified respiratory viruses in BAL specimens of patients hospitalized with lower respiratory tract infections. These viruses were associated with high morbidity, particularly in lung transplant recipients

Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV2 infection

International audienceAcute respiratory distress syndrome (ARDS) is the main complication of coronavirus disease 2019 (COVID-19), requiring admission to the intensive care unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS differs from other causes of ARDS remains unknown. To address this question, here, we build 3 cohorts of patients categorized in COVID-19ARDS, COVID-19ARDS, and COVID-19ARDS, and compare, by high-dimensional mass cytometry, their immune landscape. A cell signature associating S100A9/calprotectin-producing CD169 monocytes, plasmablasts, and Th1 cells is found in COVID-19ARDS, unlike COVID-19ARDS patients. Moreover, this signature is essentially shared with COVID-19ARDS patients, suggesting that severe COVID-19 patients, whether or not they experience ARDS, display similar immune profiles. We show an increase in CD14HLA-DR and CD14CD16 monocytes correlating to the occurrence of adverse events during the ICU stay. We demonstrate that COVID-19-associated ARDS displays a specific immune profile and may benefit from personalized therapy in addition to standard ARDS management