The viral and atypical bacterial causes of acute respiratory infection in children in Recife, Brazil

Abstract

Introduction: Acute respiratory infections (ARI) are the commonest cause of mortality in children <5 years worldwide with viral pathogens being important. The aims of MPhil year were threefold: 1) To describe the epidemiology of viral pathogens in ARI of children <5 presenting to hospital in Brazil during the emergence of novel H1N1 pandemic 2) To characterise clinical and epidemiological features of ARI in the novel group of rhinoviruses (hRV), hRV-C 3) To investigate the interaction between interleukin (IL)-17 and IL-13 in RSV infection of airway epithelial cells. Methods: 1) Multiplex PCR was utilised to test for viral (including H1N1) and atypical bacterial respiratory pathogens in nasopharyngeal aspirates from children <5 presenting with ARI to IMIP Children’s Hospital in Recife, Brazil. 2) In samples in which hRV was detected, cDNA was amplified and sequenced to compare to traditional and novel hRV strains. 3) RSV-infected and non-infected bronchial epithelial cell (BEAS-2B) cultures were simulated with IL-17, IL-13 and IL-17+IL-13. IL-6 and IL-8 were measured by ELISA in culture supernatants. Results: 1) A pathogen was identified in 88% of the 630 children recruited to this study. The most commonly detected pathogens were RSV, adenovirus, bocavirus, and hRV (33%, 29%, 24% and 19%). Co-detection occurred in 43% of samples. Influenza prevalence increased in the second year (3% vs. 15%) because of the H1N1 pandemic. Children in whom H1N1 was detected were more likely to be admitted to hospital and to be co-infected. 2) hRV was detected in 19% of ARI. We found no clinical or demographic differences between hRV ARI and non-hRV ARI. hRV ARI was more likely to present as a co-infection. The majority (84%, n=99) of samples were successfully analysed with hRV-A being the most common subtype (71%) and all remaining samples being hRV-C (21%). Children in whom hRV-C was detected were more likely to present with the diagnosis of episodic viral wheeze (EVW) / asthma. 3) In the presence of IL-17 significantly elevated IL-6 and IL-8 expression was observed at 48 hours and 24 hours respectively when BEAS-2Bs were infected with RSV. IL-13 caused no increase in IL-6 or IL-8 expression. There was no demonstrable synergy between IL-17 and IL-13. Discussion: We were able to detect a viral or atypical bacterial pathogen in most of our cohort. We highlighted the importance of the emerging pathogen H1N1, and the prevalence of co-infection. hRV was shown to be an important cause of ARI and novel hRV-C was associated with EVW/asthma. IL-17 was shown to stimulate inflammatory cytokine production, particularly during RSV infection. These findings highlight IL-17 as a potentially important cytokine in airway inflammation in RSV disease.