Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years

Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil.Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA.407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia.This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively

Respiratory Syncytial Virus Binds and Undergoes Transcription in Neutrophils From the Blood and Airways of Infants With Severe Bronchiolitis

Background. Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants

Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung

Background: Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure. This study aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airways disease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor 4 (TLR-4). Methods: The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatory infiltrate and cytokine responses were compared between wildtype mice and mice not expressing TLR-4. Results: The presence of LPS administered with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independent of TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS administered alone. Treatment with AMP induced macrophage recruitment independent of TLR-4 expression. Conclusions: These findings suggest AMP-LPS as a stronger stimulus for allergic inflammation in the airways then LPS alone.Medicine, Faculty ofNon UBCAnesthesiology, Pharmacology and Therapeutics, Department ofReviewedFacult

The Impact of the H1n1 Influenza Pandemic on Clinical Presentations and Viral Epidemiology of Acute Respiratory Infection in Preschool Children in Brazil

We assessed the impact of the H1N1 influenza pandemic on acute respiratory infection in young children from low-income families in Brazil. Influenza (specifically H1N1) detection in acute respiratory infection quintupled during the pandemic and, during its peak, it was associated with 30% of all acute respiratory infection visits to the emergency department. H1N1 was also associated with increased risk of hospitalization and coinfection

Additional oligonucleotide primers and probes used in this study.

<p>All oligonucleotides were purchased from Metabion Ltd, Germany, except MGB probes which were obtained from Applied Biosystems, Warrington, UK.</p

Pathogen prevalence (%) in nasopharyngeal aspirates from children less than five years with acute respiratory infection.

<p>Prevalence for viral/atypical pathogens and PCR negative samples is shown. Combined prevalence was greater than 100% because of co-infection. RSV, AdV, hRV and hBoV were most prevalent. (AdV, Adenoviruses; <i>Cpp</i>, <i>Chlamydia pneumoniae</i>; CoV, Coronaviruses; Flu, Influenza virus; hBoV, Bocavirus; hMPV, human Metapneumovirus; hRV, human Rhinovirus; <i>Mpp</i>, <i>Mycoplasma pneumoniae</i>; PIV, Parainfluenza virus; RSV, Respiratory syncytial virus).</p

Relationship between pathogen prevalence and ARI clinical manifestation.

<p>Most pathogens were detected in each of the four major clinical manifestation groups with prevalence being broadly similar. Only <i>Mpp</i> infection was more commonly associated with pneumonia than bronchiolitis and hBoV was more commonly associated with EVW/asthma than bronchiolitis (* p<0.05). Cumulative pathogen prevalence in each of the clinical conditions was greater than 100% because of co-infection.</p

Monthly distribution of the most frequently detected pathogens in children with ARI.

<p>RSV, hMPV and <i>Mpp</i> exhibited strong seasonal patterns, with RSV cases peaking over the rainy season (Shaded area: April-July), and hMPV and <i>Mpp</i> peaking soon afterwards (August-October).</p

Pathogen frequency in singly infected (red) and co-infected (pink) nasopharyngeal aspirate samples.

<p>The frequency with which individual pathogens were identified in single and co-infections is shown. RSV was more likely to be identified as a single pathogen whereas AdV, hBoV, hMPV and <i>Mpp</i> were more likely to be identified in co-infections.</p

Relationship between pathogen prevalence and ARI disease severity.

<p>The prevalence with which each of the pathogens was identified in different severities of disease is shown. Most pathogens were represented within each of the disease severity groups, with prevalence being broadly similar. Children with RSV were more likely to have <i>moderate</i> than mild disease compared to children without RSV infection, whilst children with <i>Mpp</i> infection were more likely to have <i>moderate</i> or <i>severe</i> than <i>mild</i> disease (* p<0.05.). Cumulative prevalence in each of the disease severity groups was greater than 100% because of co-infection.</p