Respiratory Infections In Young Children Research Articles

Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus

Respiratory syncytial virus (RSV) is the leading cause of hospitalisation for respiratory infection in young children. RSV disease severity is known to be age-dependent and highest in young infants, but other correlates of severity, particularly the presence of additional respiratory pathogens, are less well understood. In this study, nasopharyngeal swabs were collected from two cohorts of RSV-positive infants <12 months in Spain, the UK, and the Netherlands during 2017–20. We show, using targeted metagenomic sequencing of >100 pathogens, including all common respiratory viruses and bacteria, from samples collected from 433 infants, that burden of additional viruses is common (111/433, 26%) but only modestly correlates with RSV disease severity. In contrast, there is strong evidence in both cohorts and across age groups that presence of Haemophilus bacteria (194/433, 45%) is associated with higher severity, including much higher rates of hospitalisation (odds ratio 4.25, 95% CI 2.03–9.31). There is no evidence for association between higher severity and other detected bacteria, and no difference in severity between RSV genotypes. Our findings reveal the genomic diversity of additional pathogens during RSV infection in infants, and provide an evidence base for future causal investigations of the impact of co-infection on RSV disease severity.

A Hypothesis-Generating Prospective Longitudinal Study to Assess the Relative Contribution of Common Respiratory Viruses to Severe Lower Respiratory Infections in Young Children.

Respiratory viruses such as respiratory syncytial virus (RSV), influenza, parainfluenza and human metapneumovirus are well-established etiologies of acute lower respiratory tract infections (ALRIs; LRI-viruses). In contrast, adenovirus (AdV), rhinovirus/enterovirus (RV/EV) and seasonal human coronaviruses (CoV), collectively termed AdV/RV/CoV, are detected both in healthy children and children with ALRI. The methods include a prospective longitudinal case-control study, assessing the prevalence of LRI-viruses versus AdV/RV/CoV in ALRI [community-acquired alveolar pneumonia (CAAP) and bronchiolitis] during hospitalization (visit 1), 7-14 days (visit 2) and 28-35 days (visit 3) in 2-17-month-old children. Controls were 2-27-month-old children hospitalized for elective surgery during the same respiratory seasons. We enrolled 99 infants (37 CAAP, 38 bronchiolitis and 24 controls) and obtained 211 nasopharyngeal swabs. Overall, 163 (77%) had greater than or equal to 1 viruses detected; RV/EV (n = 94; 45%) and RSV (n = 71; 34%) were the most frequently detected viruses. In CAAP, the overall LRI-virus prevalence was 78.4%, 32.4% and 5.4% in visits 1, 2 and 3, respectively; the respective rates in bronchiolitis were 73.7%, 34.5% and 8.0%. In controls, no LRI-viruses were detected. In contrast, the overall AdV/RV/CoV prevalence was high among controls (70.8%) and similar among CAAP (48.6%, 40.5% and 40.5%) and bronchiolitis (47.4, 58.6% and 64.0%) across visits. Among ALRI cases, LRI-viruses dominated during the acute disease, with prevalence declining within 28-35 days, suggesting their causative role. In contrast, AdV/RV/CoV prevalence was similar during all 3 visits and in controls, suggesting that carriage of these viruses is common during the viral respiratory season. The current study is relatively small and of short duration; however, the findings are supported by other recent studies.

2156. Impact of Asymptomatic Upper Respiratory Viral Shedding in Pediatric Cardiothoracic Surgical Patients

Abstract Background Intraoperative and postoperative complications associated with symptomatic upper respiratory infections in young children are well-documented; however, asymptomatic upper respiratory viral shedding is frequent and may be prolonged. Necessary pediatric cardiac surgical procedures could be delayed with recognition of asymptomatic viral shedding. This study aimed to assess if a positive preoperative respiratory viral panel PCR (+ RVP) impacted postoperative length of stay in the pediatric intensive care unit (PICU) or hospital and assessed for an association among + RVP and adverse clinical events. Methods Patients &amp;lt; 3 years old presenting to a freestanding children’s hospital for cardiothoracic surgery from March 2018-March 2020 were enrolled. Within 24 hours before surgery, an RVP via nasopharyngeal swab for PCR was collected from subjects. Chart review was completed after hospital discharge. Mean difference between RVP status and length of stay for PICU and hospital was assessed with an independent, two group, sample t-test. Logistic regression was used to test association between RVP status and adverse clinical events (VAP, SSI, prolonged fever, ventilator use, or antibiotics), adjusted by complexity of surgical procedure using the Risk Adjustment in Congenital Heart Surgery-1 (RACHS-1) score. Results There were 95 subjects included, approximately 50% female, 75% Caucasian; 39% had + RVP (Table 1). There was no statistical association between RVP status and length of PICU (p=0.35) or hospital stay (p=0.28) (Table 2). Odds ratio for extubation in the operating room was significantly associated with +RVP, though small sample size and wide confidence intervals limit generalizability of this observation (Table 3). There were no clinically significant associations between RVP status and adverse events. Table 1.Subject DemographicsTable 2.Mean Difference in Length of Stay by RVP StatusTable 3.Odds Ratios of Clinical Adverse Events by RVP status Conclusion This limited, single-center study suggests that preoperative RVPs in pediatric cardiac surgery candidates identified asymptomatic viral shedding in 39%, though provided no detectable clinical benefit. Larger studies are needed to fully explore specific adverse clinical events and individual viral pathogen impacts. Institutional policies requiring preoperative RVP screening for pediatric cardiac surgery should be discouraged. Disclosures Kari Simonsen, MD, MBA, MedImmune: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis

SummaryBackgroundRespiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development.MethodsIn this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400).FindingsIn addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection inhospital deaths (6800–28 100), and 45700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs).InterpretationRSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented.FundingEU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Innate Immune Evasion by Human Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infection in young children. Nearly all individuals become infected in their early childhood, and reinfections with RSV are common throughout life. Primary infection with RSV is usually involved in the symptom of bronchiolitis and pneumonia in the lower respiratory tract, which accounts for over 3 million hospitalizations and approximately 66,000 deaths annually worldwide. Despite the widespread prevalence and high morbidity and lethality rates of diseases caused by RSV infection, there is currently no licensed RSV vaccine. During RSV infection, innate immunity plays the first line of defense to suppress RSV infection and replication. However, RSV has evolved multiple mechanisms to evade the host’s innate immune responses to gain a window of opportunity for efficient viral replication. This review discusses the comprehensive interaction between RSV infection and the host antiviral innate immunity and updates recent findings on how RSV modulates the host innate immune response for survival, which may provide novel insights to find potent drug targets and vaccines against RSV.

Outbreak of Parainfluenza Virus During the COVID-19 Pandemic at a University Hospital in Korea.

The incidence of respiratory viral diseases including parainfluenza virus (PIV) infection has decreased noticeably due to strict quarantine measures during the COVID-19 pandemic. However, the recent outbreak of PIV in children occurred unexpectedly and the distribution pattern showed prominent differences from before the COVID-19 pandemic. PIV is one of the major viral pathogens related to acute lower respiratory infection in young children and the elderly. Accordingly, the authors intended to identify the incidence and distribution pattern of PIV outbreaks and to contribute to public health by providing information on it. This study was conducted retrospectively to investigate the incidence and distribution of PIV according to age group, gender, month, and season, and to analyze the co-infections from March 2020 to February 2022. The detection for respiratory microorganisms was performed through FilmArray assay. The overall incidence for at least one respiratory pathogen was 45.9% (665/1,450). PIV was not detected at all from March 2020 to August 2021. However, it was first detected in September 2021 and the rate in the month that followed, October, accounted for 60% (114/190) of the total PIV infections during the entire study period. It also accounted for 44.9% (190/423) of patients with respiratory pathogens from September 2021 to February 2022. It reached the highest proportion at 90.5% (114/126) in October 2021. As for the distribution according to the age groups, group 3 (58.4%) accounted for the highest percentage, followed by group 4 (21.1%). In the PIV positive cases, the overall rate of more than two respiratory pathogens was 32.6% (62/190). The most common pattern of co-infection was PIV3 with rhinovirus/enterovirus (67.7%), followed by PIV3 with adenovirus (8.1%) and PIV3 with rhinovirus/enterovirus and adenovirus (8.1%). The COVID-19 pandemic has brought about many changes in our daily lives. It has been confirmed that the seasonal distribution of PIV was distinctly different from before the COVID-19 pandemic. It is anticipated that this phenomenon will affect the incidence or distribution of other respiratory pathogens and viral epidemiology. Therefore, clinicians should pay attention to these changes in terms of public health.

Glutathione (GSH) and superoxide dismutase (SOD) levels among junior high school students induced by indoor particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) exposure.

Background: Indoor air pollution has globally known as the risk factor of acute respiratory infection in young children. The exposure to indoor particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) at house or school can be a potential risk to children’s health. This study aimed to examine the association between indoor PM2.5 and NO2 with oxidative stress markers in junior high school students.Design and methods: This study was conducted using a cross sectional study with 75 students collected randomly from four junior high schools in Jakarta. PM2.5 and NO2 were measured in classrooms and school yards. The schools were categorized based on the exposure level of PM2.5 and NO2 in classrooms. Superoxide dismutase (SOD) and reduced glutathione (GSH) were examined from the blood sample. All students were interviewed with questionnaires to determine upper respiratory tract infection, smoking family members, mosquito repellent usage, and dietary supplement consumption.Results: Mean concentration of indoor PM2.5 and NO2 were 0.125±0.036 mg m-3 and 36.37±22.33 μg m-3, respectively. The schools which located near to highway showed lower PM2.5 and higher NO2 level indicated the emission of traffic activity. Mean activity of SOD was 96.36±50.94 U mL-1 and mean concentration of GSH was of 0.62±0.09 μg mL-1. Most of the students reported upper respiratory tract infection history, smoking family member, use mosquito repellent at home, and do not consume dietary supplement.Conclusions: The level of oxidative stress markers and the exposure categories of classroom PM2.5 and NO2 was not significantly different, however there were significant correlation with cigarette smoke and mosquito repellent at home. Nevertheless, the exposure of indoor PM2.5 and NO2 increased the risk of the exposure to cigarette smoke and mosquito repellent at home. Further study on the air pollution at school and home is needed to affirm association towards student’s health and to design strategic control efforts. Significance for public health Indoor air pollution has globally known as one of public health problem and the risk factor of acute respiratory infection in young children. The exposure to indoor particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) at house or school can be a potential risk to children’s health. This study aimed to examine the association between indoor PM2.5 and NO2 with oxidative stress markers in junior high school students and help affirm association towards student’s health and to design strategic control efforts.

Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection.

Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally. We have developed a method to generate alveolar-like macrophages (ALMs) from pluripotent stem cells. These ALMs have shown potential to promote airway innate immunity and tissue repair and so we hypothesized that ALMs could be used as a strategy to prevent RSV infection. Here, we demonstrate that ALMs are not productively infected by RSV and prevent the infection of epithelial cells. Prevention of epithelial infection was mediated by two different mechanisms: phagocytosis of RSV particles and release of an antiviral soluble factor different from type I interferon. Furthermore, intratracheal administration of ALMs protected mice from subsequent virus-induced weight loss and decreased lung viral titres and inflammation, indicating that ALMs can impair the pathogenesis of RSV infection. Our results support a prophylactic role for ALMs in the setting of RSV infection and warrant further studies on stem cell-derived ALMs as a novel cell-based therapy for pulmonary viral infections.

Chest X-ray lung imaging features in pediatric COVID-19 and comparison with viral lower respiratory infections in young children.

RationaleChest radiography (CXR) is a noninvasive imaging approach commonly used to evaluate lower respiratory tract infections (LRTIs) in children. However, the specific imaging patterns of pediatric coronavirus disease 2019 (COVID‐19) on CXR, their relationship to clinical outcomes, and the possible differences from LRTIs caused by other viruses in children remain to be defined.MethodsThis is a cross‐sectional study of patients seen at a pediatric hospital with polymerase chain reaction (PCR)‐confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (n = 95). Patients were subdivided in infants (0–2 years, n = 27), children (3–10 years, n = 27), and adolescents (11–19 years, n = 41). A sample of young children (0–2 years, n = 68) with other viral lower respiratory infections (LRTI) was included to compare their CXR features with the subset of infants (0–2 years) with COVID‐19.ResultsForty‐five percent of pediatric patients with COVID‐19 were hospitalized and 20% required admission to intensive care unit (ICU). The most common abnormalities identified were ground‐glass opacifications (GGO)/consolidations (35%) and increased peribronchial markings/cuffing (33%). GGO/consolidations were more common in older individuals and perihilar markings were more common in younger subjects. Subjects requiring hospitalization or ICU admission had significantly more GGO/consolidations in CXR (p < .05). Typical CXR features of pediatric viral LRTI (e.g., hyperinflation) were more common in non‐COVID‐19 viral LRTI cases than in COVID‐19 cases (p < .05).ConclusionsCXR may be a complemental exam in the evaluation of moderate or severe pediatric COVID‐19 cases. The severity of GGO/consolidations seen in CXR is predictive of clinically relevant outcomes. Hyperinflation could potentially aid clinical assessment in distinguishing COVID‐19 from other types of viral LRTI in young children.

Depletion of TAX1BP1 Amplifies Innate Immune Responses during Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the main cause of acute respiratory infections in young children and also has a major impact on the elderly and immunocompromised people. In the absence of a vaccine or efficient treatment, a better understanding of RSV interactions with the host antiviral response during infection is needed. Previous studies revealed that cytoplasmic inclusion bodies (IBs), where viral replication and transcription occur, could play a major role in the control of innate immunity during infection by recruiting cellular proteins involved in the host antiviral response. We recently showed that the morphogenesis of IBs relies on a liquid-liquid-phase separation mechanism depending on the interaction between viral nucleoprotein (N) and phosphoprotein (P). These scaffold proteins are expected to play a central role in the recruitment of cellular proteins to IBs. Here, we performed a yeast two-hybrid screen using RSV N protein as bait and identified the cellular protein TAX1BP1 as a potential partner of this viral protein. This interaction was validated by pulldown and immunoprecipitation assays. We showed that TAX1BP1 suppression has only a limited impact on RSV infection in cell cultures. However, RSV replication is decreased in TAX1BP1-deficient (TAX1BP1 knockout [TAX1BP1KO]) mice, whereas the production of inflammatory and antiviral cytokines is enhanced. In vitro infection of wild-type or TAX1BP1KO alveolar macrophages confirmed that the innate immune response to RSV infection is enhanced in the absence of TAX1BP1. Altogether, our results suggest that RSV could hijack TAX1BP1 to restrain the host immune response during infection. IMPORTANCE Respiratory syncytial virus (RSV), which is the leading cause of lower respiratory tract illness in infants, remains a medical problem in the absence of a vaccine or efficient treatment. This virus is also recognized as a main pathogen in the elderly and immunocompromised people, and the occurrence of coinfections (with other respiratory viruses and bacteria) amplifies the risks of developing respiratory distress. In this context, a better understanding of the pathogenesis associated with viral respiratory infections, which depends on both viral replication and the host immune response, is needed. The present study reveals that the cellular protein TAX1BP1, which interacts with the RSV nucleoprotein N, participates in the control of the innate immune response during RSV infection, suggesting that the N-TAX1BP1 interaction represents a new target for the development of antivirals.

Unraveling the Impact of Pneumococcal Conjugate Vaccines on Ambulatory Antibiotic Drug Consumption in Young Children: An Interrupted Time-Series Analysis.

Pneumococcal conjugate vaccines (PCVs) reduce respiratory infections in young children, the main antibiotic consumers. Following PCV implementation, dispensed antibiotic prescription (DAP) rates in young children were expected to decline. Computerized data on DAP for children <5 years were examined during a 13-year period (including 4 pre-PCV years). All DAPs from clinics with ≥50 insured children, active both pre- and post-PCV implementation were included. Interrupted time-series with segmented regression was applied to analyze monthly DAP rate trends, adjusted for age, ethnicity, and season. Incidence rate ratios (IRRs) of DAPs during the late PCV13 period versus 4 years pre-PCV were calculated both as absolute rate ratios (aIRRs) and relative to expected rates (rIRRs). Of 1 090 870 DAPs, 57% were in children <2 years. All-DAP rates peaked in the cold season. Post-PCV7/PCV13 implementation, all DAP rates abruptly and significantly declined, reaching a plateau within 5 years. This was largely driven by amoxicillin/amoxicillin-clavulanate (75% of DAPs). Age <2 years and Bedouin ethnicity were significantly associated with higher pre-PCV DAP rates but with faster and greater decline post-PCV, achieving near elimination of gaps between ages and ethnic groups. Overall reduction (95% CIs) in DAP rates per 1000 was estimated between aIRR (344.7 [370.9-358.4]) and rIRR (110.4 [96.9-123.7]) values. Shortly following PCV implementation, overall DAP rates showed an abrupt, steep decline, stabilizing within 5 years, in parallel to post-PCV respiratory infection trends previously described in this population, suggesting causality. The variable patterns of certain drug categories suggest additional influences beyond PCV.

Costs of acute respiratory infections in young children are high in Malaysia

Costs of acute respiratory infections in young children are high in Malaysia

Impact of compliance with cholecalciferol administration on the incidence of respiratory infections in young children

Introduction . Data on the vitamin D receptors (VDR) found on the surface of a large number of cell types of the human body were first published several decades ago, which served as a prerequisite to study the role of vitamin D in the development of some diseases, including infections. Objective of the study . Evaluate the relationship between administration of cholecalciferol supplements, the synthesis of defensins, and the incidence and morbidity patterns of acute respiratory infections (ARI) in young children. Material and methods. 108 healthy children aged 1 month to 3 years were examined, of which 34 (31.5%) were vitamin D sufficient, 40 (37.0%) had a vitamin D insufficiency, 27 (25.0%) had a vitamin D deficiency and 7 (6.5%) children had severe vitamin D deficiency. After the course of treatment of vitamin D deficiency with therapeutic doses, all patients were prescribed prophylactic doses of cholecalciferol supplements (1000 IU/day) for a 6-month course. Results. Therapeutic doses of cholecalciferol promoted β 1 and β 2-defensin expression; a direct correlation was found between the daily dose of vitamin D and the increase of β 2-defensin expression (r = 0.34, p <0.05). Administration of cholecalciferol in the prophylactic dose of 1000 IU/day for 6 months was accompanied by the further increase in antimicrobial peptide (AMP) production, which resulted in the increase of the β 1-defensin level by 2.4 times (p <0.001) and β 2-defensin level by 2.5 times (p <0.001) as compared with the baseline levels. The incidence of respiratory morbidity amounted to 1.7 ± 0.2 episodes every 6 months against the background of ongoing cholecalciferol supplementation. The number of patients, who were not infected, was significantly more in the group of children with optimal vitamin D status, than in the groups of children with vitamin D insufficiency and deficiency. Conclusions . Administration of vitamin D supplements induces antimicrobial peptide expression and reduces the frequency and severity of acute respiratory infections in young children.

Comprehensive Lipidomic and Metabolomic Analysis for Studying Metabolic Changes in Lung Tissue Induced by a Vaccine against Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in young children. Although the disease may be severe in immunocompromised, young, and elderly people, there is currently no approved vaccine. We previously reported the development and immunological assessment of a novel intranasal vaccine formulation consisting of a truncated version of the RSV fusion protein (ΔF) combined with a three-component adjuvant (TriAdj). Now, we aim to investigate the mechanism of action of the ΔF/TriAdj formulation by searching for metabolic alterations caused by intranasal immunization and the RSV challenge. We carried out untargeted lipidomics and submetabolome profiling (carboxylic acids and amine/phenol-containing metabolites) of lung tissue from ΔF/TriAdj-immunized and nonimmunized, RSV-challenged mice. We observed significant changes of lipids involved in the lung surfactant layer for the nonimmunized animals compared to healthy controls but not for the immunized mice. Metabolic pathways involving the synthesis and regulation of amino acids and unsaturated fatty acids were also modulated by immunization and the RSV challenge. This study illustrates that lipidomic and metabolomic profiling could provide a more comprehensive understanding of the immunological and metabolic alterations caused by RSV and the modulation effected by the ΔF/TriAdj formulation.

Hospitalizations for lower respiratory tract infections in children in relation to the sequential use of three pneumococcal vaccines in Quebec.

In Quebec, three pneumococcal conjugate vaccines (PCV) were used sequentially starting in December 2004. The objective of the study was to investigate the association between exposure to different PCV regimens and hospitalizations for lower respiratory tract infection (LRTI). Records with a main diagnosis of LRTI in children born in 2000-2012 and observed up to their second birthday were extracted from the provincial hospital administrative database. Main vaccine regimen in different birth cohorts was derived from the Quebec City Immunization Registry. Hospital admission risk was analyzed by Poisson regression models adjusting for age, season of birth, ambient air temperature, circulation of respiratory viruses, and the weekly hospital admission rate for all other causes excluding LRTI to control for temporal changes in hospital admission practices. In univariate analyses, hospitalizations for LRTI, pneumonia, and bronchiolitis were less frequent in cohorts exposed to PCVs than in unvaccinated cohorts with no difference between PCV regimens. For pneumonia, the difference in cumulative incidence was 16% (13%; 18%). In multivariate analyses, exposure to any PCV schedule was associated with a lower although statistically non-significant hospitalization risk for pneumonia ascompared with unvaccinated cohorts. Again, differences between PCV regimens were minimal. Interpretation of results of this ecological study should be made with care as many factors could influence hospitalizations for respiratory infection in young children. Results are compatible with a modest effect of PCVs in reducing hospitalizations for pneumonia in children. No substantial differences between various PCV schedules were observed.

Airway mir-155 responses are associated with TH1 cytokine polarization in young children with viral respiratory infections.

BackgroundMicroRNAs (miRs) control gene expression and the development of the immune system and antiviral responses. MiR-155 is an evolutionarily-conserved molecule consistently induced during viral infections in different cell systems. Notably, there is still an unresolved paradox for the role of miR-155 during viral respiratory infections. Despite being essential for host antiviral TH1 immunity, miR-155 may also contribute to respiratory disease by enhancing allergic TH2 responses and NFkB-mediated inflammation. The central goal of this study was to define how airway miR-155 production is related to TH1, TH2, and pro-inflammatory cytokine responses during naturally occurring viral respiratory infections in young children.MethodsNormalized nasal airway levels of miR-155 and nasal protein levels of IFN-γ, TNF-α, IL-1β, IL-13, IL-4 were quantified in young children (≤2 years) hospitalized with viral respiratory infections and uninfected controls. These data were linked to individual characteristics and respiratory disease parameters.ResultsA total of 151 subjects were included. Increased miR-155 levels were observed in nasal samples from patients with rhinovirus, RSV and all respiratory viruses analyzed. High miR-155 levels were strongly associated with high IFN-γ production, increased airway TH1 cytokine polarization (IFN-γ/IL-4 ratios) and increased pro-inflammatory responses. High airway miR-155 levels were linked to decreased respiratory disease severity in individuals with high airway TH1 antiviral responses.ConclusionsThe airway secretion of miR-155 during viral respiratory infections in young children is associated with enhanced antiviral immunity (TH1 polarization). Further studies are needed to define additional physiological roles of miR-155 in the respiratory tract of human infants and young children during health and disease.

The burden of viral respiratory infections in young children in low-resource settings

The burden of viral respiratory infections in young children in low-resource settings

The Interactome analysis of the Respiratory Syncytial Virus protein M2-1 suggests a new role in viral mRNA metabolism post-transcription

Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic polyA-binding protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.

Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal.

ProblemRhinoviruses (RVs), the most common causes of acute respiratory infections in young children and infants, are highly diverse genetically.ObjectiveTo characterize the RV types detected with respiratory illness episodes in infants in Nepal.Study methodsInfants born to women enrolled in a randomized trial of maternal influenza immunization in rural, southern Nepal were followed with household‐based weekly surveillance until 180 days of age. Infants with respiratory symptoms had nasal swabs tested for twelve respiratory viruses. A subset with RV alone was selected for sequencing of the VP4/2 gene to identify RV types.ResultsAmong 547 RV‐only positive illnesses detected from December 2012 to April 2014, 285 samples (52%) were sequenced. RV‐A, B, and C species were detected in 193 (68%), 18 (6%), and 74 (26%) specimens, respectively. A total of 94 unique types were identified from the sequenced samples, including 52 RV‐A, 11 RV‐B, and 31 RV‐C. Multiple species and types circulated simultaneously throughout the study period. No seasonality was observed. The median ages at illness onset were 88, 104, and 88 days for RV‐A, B, and C, respectively. The median polymerase chain reaction cycle threshold values did not differ between RV species. No differences between RV species were observed for reported respiratory symptoms, including pneumonia, or for medical care‐seeking.ConclusionsAmong very young, symptomatic infants in rural Nepal, all three species and many types of RV were identified; RV‐A was detected most frequently. There was no association between RV species and disease severity.

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]). This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).