RSV disease severity in children
The article we suggest this week - Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection, published last November on Am J Respir Crit Care Med - aims at assessing whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.
SUMMARY:Globally, respiratory syncytial virus (RSV) is the most frequent viral cause of acute lower respiratory infections in children younger than 5 years of age, and it is responsible for significant morbidity worldwide and mortality in infants in the developing world. Disease severity in these infants has been linked to a dysregulated host immune response. Besides the direct virus–host interaction, certain bacterial members of the respiratory tract microbiome might influence host responses to RSV, therewith modulating inflammation and possibly disease severity. Recent reports suggest that the composition of the nasopharyngeal microbiome affects the overall risk of developing respiratory tract infections and is associated with the severity of acute respiratory symptoms. So, the authors conducted a prospective observational study in order to characterize the nasopharyngeal microbiota, using 16S-rRNA–based sequencing and analyzed whole-blood RNA transcriptional profiles in outpatients with RSV and infants hospitalized with an RSV infection, as well as healthy control subjects. They defined the nasopharyngeal microbiota profiles in infants with RSV disease and their relationship with host immune responses and disease severity.A total of 132 children, 106 with RSV infection and 26 healthy control subjects, were enrolled. Overall, children hospitalized with RSV infection were younger than outpatients with RSV and healthy control subjects. The inpatients were treated with antibiotics more frequently than outpatients (P < 0.0005).The authors identified five 'major' Operational taxonomic Units (OTUs), including Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus and five minor classifier taxa. The abundance of H. influenzae and Streptococcus OTUs was positively associated with RSV hospitalization (P = 0.005 and P = 0.004, respectively), whereas S. aureus abundance was inversely associated with the need for hospitalization (P = 0.025). In addition, high abundance of Moraxella was observed most often in outpatients (P = 0.034).Data revealed an increased expression of IFN-related modules in patients with RSV, regardless of the microbiota profiles. However, expression of inflammation modules were higher in the H. influenzae–and Streptococcus-dominated clusters compared with the S. aureus cluster. In contrast, B cell, T cell, and cytotoxic/natural killer cell modules were overall underexpressed, which was particularly evident for the H. influenzae– and Streptococcus-enriched clusters. Last, there were differences in median expression values of inflammation and neutrophil module–associated genes between the different clusters. Data showed an additive effect of the presence of Streptococcus and H. influenzae on the RSV-induced host immune response, characterized by stronger activation of inflammatory pathways, which in turn might be related to a more severe RSV disease phenotype.The authors observed that infants within H. influenzae– and Streptococcus enriched clusters mounted a distinct host inflammatory response characterized by overexpression of genes related to TLR signaling and neutrophil recruitment and activation, as compared with children with another microbiota composition, particularly those in the S. aureus cluster. This study was the first to assess the interrelation between the upper respiratory tract microbiome and the host systemic transcriptome immune response in young children with RSV infection and to document how these interactions might influence the clinical disease phenotype.The authors concluded that a nasopharyngeal microbiota composition, characterized by H. influenzae and Streptococcus as opposed to S. aureus, is associated with a distinct host inflammatory immune response and enhanced disease severity as defined by more frequent need for RSV hospitalization.
AUTHORS: W.A. de Steenhuijsen Piters, S. Heinonen, R. Hasrat, E. Bunsow, B. Smith, M.C. Suarez-Arrabal, D. Chaussabel, D.M. Cohen, E.A. Sanders, O. Ramilo, D. Bogaert, A. Mejias
Kawasaki Disease in Portugal
The reading WAidid recommends this week is a recent article published on Pediatric Infectious Disease Journal 2016 Nov 30, "Twelve Years of Kawasaki Disease in Portugal: Epidemiology in Hospitalized Children".
SUMMARY:Kawasaki disease (KD) is an acute febrile illness with multisystemic vasculitis that predominantly occurs in children under 5 years of age with a male predominance. It has now been reported worldwide in all ethnic and racial groups, but with significant different incidence rates. KD is the leading cause of acquired heart disease in developed countries.The etiology of the disease remains unknown, despite 4 decades of research. The leading hypothesis is that KD reflects an abnormal inflammatory response to one or more infectious triggers and environment factors in genetically susceptible individuals.The first case of KD in Portugal was reported in 1981. In 2001 the Portuguese Pediatric Society started a Pediatric surveillance unit for KD, whose adherence was considered suboptimal. For this reason, the authors started an extended study protocol for KD patients follow up, specially focused on long term cardiovascular sequelae, endothelial function and precursors of atherosclerosis evaluation. In this study the authors analyzed data from the national database of hospital discharge diagnostic codes regarding hospitalized children classified with KD code for a period of 12 years (2000 - 2011). Using these data, they estimated the number of the KD hospitalizations, the number of patients with the disease and the mean annual incidences of KD among children in Portugal.A total of 533 hospitalizations were registered among 470 individuals aged less than 20 years in Portugal: 393 patients were grouped <5 years of age (85%) and 109 in the subgroup less than 1 year old (23%). The mean age at admission of all patients was 2.8 years and 61% of patients were male; 58,9% patients were hospitalized in the Lisbon region. The mean length of hospital stay was 9 days. The incidence peaked in the spring months (35%) and the vast majority during spring/winter (63% of cases) months. During the studied period there was an average of 39 new patients of KD per year, and four peaks of total hospitalized patients, years 2000, 2004, 2008 and 2011.Cardiac involvement was reported in 12.9% of patients, predominately in male (P= 0.001). The most frequent cardiac lesion was the development of coronary artery aneurysms (CAA), followed by pericarditis, mitral valvulitis, and supraventricular tachycardia. The vast majority of cases with CAA occurred in children younger than 5 years of age and in the subgroup of children aged 1-4 years. There were two deaths (0.4%), attributed to myocardial infarction.The general population incidence of KD was 1.9 per 100,000 individuals, with the highest incidence in children under 5 years old (6.48 per 100,000 children), followed by older children (1.1 per 100,000 children), and almost null for patients older than 9 years old.The incidence of KD was significantly higher in boys, with the highest rate occurring in male infants under 1 year of age (11.4 per 100,000).The incidence of KD was higher in the regions with a higher density of population.Although the authors themselves highlighted some limitations, this was the first large scale epidemiological study of KD in Portugal, which provides a national estimate of hospitalizations associated with physician-diagnosed KD among Portuguese children.
AUTHORS: Fátima F. Pinto, Sérgio Laranjo, Miguel Mota Carmo, Maria João Brito, Rui Cruz Ferreira