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A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Background: The South African government employed various nonpharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2. Surveillance data from South Africa indicates reduced circulation of respiratory syncytial virus (RSV) throughout the 2020–2021 seasons. Here, we use a mechanistic transmission model to project the rebound of RSV in the two subsequent seasons. Methods: We fit an age-structured epidemiological model to hospitalization data from national RSV surveillance in South Africa, allowing for time-varying reduction in RSV transmission during periods of COVID-19 circulation. We apply the model to project the rebound of RSV in the 2022 and 2023 seasons. Results: We projected an early and intense outbreak of RSV in April 2022, with an age shift to older infants (6–23 months old) experiencing a larger portion of severe disease burden than typical. In March 2022, government alerts were issued to prepare the hospital system for this potentially intense outbreak. We then assess the 2022 predictions and project the 2023 season. Model predictions for 2023 indicate that RSV activity has not fully returned to normal, with a projected early and moderately intense wave. We estimate that NPIs reduced RSV transmission between 15% and 50% during periods of COVID-19 circulation. Conclusions: A wide range of NPIs impacted the dynamics of the RSV outbreaks throughout 2020–2023 in regard to timing, magnitude, and age structure, with important implications in a low- and middle-income countries (LMICs) setting where RSV interventions remain limited. More efforts should focus on adapting RSV models to LMIC data to project the impact of upcoming medical interventions for this disease.

BACKGROUND Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection. METHODS In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein–based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated. RESULTS A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR–confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory

Although bovine respiratory syncytial virus (BRSV) infection has been reported in cattle in Argentina, it has not been associated with pneumonia in Argentina. We report here 5 cases of bovine pneumonia associated with BRSV. Autopsies were performed on 35 beef cattle with gross and/or microscopic lesions of pneumonia from 3 commercial feedlots. Lung samples in 5 of 35 animals were BRSV-positive by reverse-transcription nested PCR. The lungs of 2 of these 5 animals were coinfected with Mannheimia haemolytica, and 1 with bovine viral diarrhea virus 1. Microscopically, the lungs of 3 of the 5 BRSV PCR-positive animals had fibrinosuppurative bronchopneumonia, with or without pleuritis; 2 of the 5 had interstitial pneumonia. We conclude that BRSV is part of the bovine respiratory disease complex in Argentina.

Background: Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. Methods: We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations in <5-year-olds were used as proxies for relative weekly viral activity. Results: From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in <5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. Conclusions: RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF. RESULTS: 2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6). CONCLUSIONS: Adults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of children, the elderly, and immunocompromised individuals. Currently, there are no FDA-approved RSV vaccines. The RSV G glycoprotein is used for viral attachment to host cells and impairment of host immunity by interacting with the human chemokine receptor CX3CR1. Antibodies that disrupt this interaction are protective against infection and disease. Nevertheless, development of an RSV G vaccine antigen has been hindered by its low immunogenicity and safety concerns. A previous study described three engineered RSV G proteins containing single-point mutations that induce higher levels of IgG antibodies and have improved safety profiles compared to wild-type RSV G (H. C. Bergeron, J. Murray, A. M. Nuñez Castrejon, et al., Viruses 13:352, 2021, https://doi.org/10.3390/v13020352). However, it is unclear if the mutations affect RSV G protein folding and display of its conformational epitopes. In this study, we show that the RSV G S177Q protein retains high-affinity binding to protective human and mouse monoclonal antibodies and has equal reactivity as wild-type RSV G protein to human reference immunoglobulin to RSV. Additionally, we determined the high-resolution crystal structure of RSV G S177Q protein in complex with the anti-RSV G antibody 3G12, further validating its antigenic structure. These studies show for the first time that an engineered RSV G protein with increased immunogenicity and safety retains conformational epitopes to high-affinity protective antibodies, supporting its further development as an RSV vaccine immunogen. IMPORTANCE Respiratory syncytial virus (RSV) causes severe lower respiratory diseases of children, the elderly, and immunocompromised populations. There currently are no FDA-approved RSV vaccines. Most vaccine development efforts have focused on the RSV F protein, and the field has generally overlooked the receptor-binding antigen RSV G due to it

SignificanceStrategies to reduce consumption of antimicrobial drugs are needed to contain the growing burden of antimicrobial resistance. Respiratory syncytial virus (RSV) is a prominent cause of upper and lower respiratory tract infections, as a single agent and in conjunction with bacterial pathogens, and may thus contribute to the burden of both inappropriately treated viral infections and appropriately treated polymicrobial infections involving bacteria. In a double-blind, randomized, placebo-controlled trial, administering an RSV vaccine to pregnant mothers reduced antimicrobial prescribing among their infants by 12.9% over the first 3 mo of life. Our findings implicate RSV as an important contributor to antimicrobial exposure among infants and demonstrate that this exposure is preventable by use of effective maternal vaccines against RSV.

Seasonal epidemics of influenza and the respiratory syncytial virus (RSV) are the cause of substantial morbidity and mortality among children. During the global coronavirus disease 2019 (COVID-19) pandemic, the epidemiology of these viruses seems to have changed dramatically. In Australia and New Zealand, a significant decrease in both influenza and bronchiolitis have been noticed during usual peak seasons. Data from early months of winter seasons in Europe are showing similar trends. This current scenario imposes a reconsideration of the paradigm that toddlers and young schoolchildren are the main drivers of seasonal RSV outbreaks and respiratory epidemics in general. In this article, we summarize current literature, address current knowledge or role of adults in the RSV epidemiology, describe the lessons learned from pertussis epidemics and call the international community to better understand the community transmission dynamics of respiratory infections in all age groups. This can allow the establishment of better and more affordable preventive measures in the whole population level, which can ultimately save millions of child lives.

The efficacy and safety of nirsevimab in the treatment of medically attended respiratory syncytial virus (RSV) infections of the lower respiratory tract in otherwise healthy, late preterm and term infants were assessed in the phase 2B1 and phase 3 MELODY2 trials. An ongoing phase 2–3 trial (ClinicalTrials.gov number, NCT03959488. opens in new tab) is evaluating the safety and pharmacokinetics of nirsevimab in infants at risk for severe RSV infection of the lower respiratory tract who are eligible to receive palivizumab. [...]

PurposeBronchiolitis is a very common acute lung disease in infants caused commonly by respiratory syncytial virus (RSV). Point-of-care lung ultrasound is increasingly used in clinical care but proof that ultrasound reflects histological disease is lacking. Bovine calves are a good model for RSV bronchiolitis. We answered the following two questions: (1) does point-of-care lung ultrasound reflect lung pathology at the histological level in a bovine calf model of bronchiolitis? and (2) are point-of-care lung ultrasound images in human infants similar to those obtained in calves?MethodsWe experimentally infected 24 five to six-week-old bovine calves with RSV and compared six window lung ultrasound with lung histology10 days after inoculation. The calves were treated with antivirals and antipyretics leading to variable severity of illness. We used canonical discriminant analysis to determine if abnormal lung ultrasound findings reflected different histological findings. We compared the ultrasounds obtained from the calves with ultrasounds obtained from 10 human infants who were diagnosed clinically with bronchiolitis.ResultsCanonical discriminant analysis generally demonstrated good class separation based on the maximal severity of ultrasound finding in each acoustic window. Lung ultrasound performed poorly at detecting bronchopneumonia. Bovine ultrasounds looked similar to human infant lung ultrasounds.ConclusionPoint-of-care lung ultrasound abnormalities reflect lung pathology at the histological level in a bovine calf model of bronchiolitis. Point-of-care lung ultrasound images in human infants are similar to those obtained in calves.

SignificanceStrategies to reduce consumption of antimicrobial drugs are needed to contain the growing burden of antimicrobial resistance. Respiratory syncytial virus (RSV) is a prominent cause of upper and lower respiratory tract infections, as a single agent and in conjunction with bacterial pathogens, and may thus contribute to the burden of both inappropriately treated viral infections and appropriately treated polymicrobial infections involving bacteria. In a double-blind, randomized, placebo-controlled trial, administering an RSV vaccine to pregnant mothers reduced antimicrobial prescribing among their infants by 12.9% over the first 3 mo of life. Our findings implicate RSV as an important contributor to antimicrobial exposure among infants and demonstrate that this exposure is preventable by use of effective maternal vaccines against RSV.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of children, the elderly, and immunocompromised individuals. Currently, there are no FDA-approved RSV vaccines. The RSV G glycoprotein is used for viral attachment to host cells and impairment of host immunity by interacting with the human chemokine receptor CX3CR1. Antibodies that disrupt this interaction are protective against infection and disease. Nevertheless, development of an RSV G vaccine antigen has been hindered by its low immunogenicity and safety concerns. A previous study described three engineered RSV G proteins containing single-point mutations that induce higher levels of IgG antibodies and have improved safety profiles compared to wild-type RSV G (H. C. Bergeron, J. Murray, A. M. Nuñez Castrejon, et al., Viruses 13:352, 2021, https://doi.org/10.3390/v13020352). However, it is unclear if the mutations affect RSV G protein folding and display of its conformational epitopes. In this study, we show that the RSV G S177Q protein retains high-affinity binding to protective human and mouse monoclonal antibodies and has equal reactivity as wild-type RSV G protein to human reference immunoglobulin to RSV. Additionally, we determined the high-resolution crystal structure of RSV G S177Q protein in complex with the anti-RSV G antibody 3G12, further validating its antigenic structure. These studies show for the first time that an engineered RSV G protein with increased immunogenicity and safety retains conformational epitopes to high-affinity protective antibodies, supporting its further development as an RSV vaccine immunogen. IMPORTANCE Respiratory syncytial virus (RSV) causes severe lower respiratory diseases of children, the elderly, and immunocompromised populations. There currently are no FDA-approved RSV vaccines. Most vaccine development efforts have focused on the RSV F protein, and the field has generally overlooked the receptor-binding antigen RSV G due to it

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection with the most severe disease in the young and elderly. Non-pharmaceutical interventions and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated regions of the Australian continent, New South Wales (NSW) and Australian Capital Territory (ACT) in the east, and Western Australia. Through genomic sequencing we reveal a major reduction in RSV genetic diversity following COVID-19 emergence with two genetically distinct RSV-A clades circulating cryptically, likely localised for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria and to cause extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic, as mitigation measures may disrupt seasonal patterns, causing larger or more severe outbreaks.

Bronchiolitis due to respiratory syncytial virus (RSV) or non-RSV agents is a health-menacing lower respiratory tract (LRT) disease of infants. Whereas RSV causes more severe disease than other viral agents may, genus-dominant fecal microbiota profiles have been identified in US hospitalized infants with bronchiolitis. We investigated the fecal microbiota composition of infants admitted to an Italian hospital with acute RSV (25/37 [67.6%]; group I) or non-RSV (12/37 [32.4%]; group II) bronchiolitis, and the relationship of fecal microbiota characteristics with the clinical characteristics of infants. Group I and group II infants differed significantly (24/25 [96.0%] versus 5/12 [41.7%]; P = 0.001) regarding 90% oxygen saturation (SpO2), which is an increased respiratory effort hallmark. Accordingly, impaired feeding in infants from group I was significantly more frequent than in infants from group II (19/25 [76.0%] versus 4/12 [33.3%]; P = 0.04). Conversely, the median (IQR) length of stay was not significantly different between the two groups (seven [3–14] for group I versus five [5–10] for group II; P = 0.11). The 16S ribosomal RNA V3–V4 region amplification of infants’ fecal samples resulted in 299 annotated amplicon sequence variants. Based on alpha- and beta-diversity microbiota downstream analyses, group I and group II infants had similar bacterial communities in their samples. Additionally, comparing infants having <90% SpO2 (n = 29) with infants having ≥90% SpO2 (n = 8) showed that well-known dominant genera (Bacteroides, Bifidobacterium, Escherichia/Shigella, and Enterobacter/Veillonella) were differently, but not significantly (P = 0.44, P = 0.71, P = 0.98, and P = 0.41, respectively) abundant between the two subgroups. Overall, we showed that, regardless of RSV or non-RSV bronchiolitis etiology, no fecal microbiota-composing bacteria could be associated with the severity of acute bronchiolitis in infants. Larger and longitudinally conducted studies wil

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.

Respiratory syncytial virus (RSV) infection can cause bronchiolitis, pneumonia, morbidity, and some mortality, primarily in infants and the elderly, for which no vaccine is available. The RSV attachment (G) protein contains a central conserved domain (CCD) with a CX3C motif implicated in the induction of protective antibodies, thus vaccine candidates containing the G protein are of interest. This study determined if mutations in the G protein CCD would mediate immunogenicity while inducing G protein CX3C-CX3CR1 blocking antibodies. BALB/c mice were vaccinated with structurally-guided, rationally designed G proteins with CCD mutations. The results show that these G protein immunogens induce a substantial anti-G protein antibody response, and using serum IgG from the vaccinated mice, these antibodies are capable of blocking the RSV G protein CX3C-CX3CR1 binding while not interfering with CX3CL1, fractalkine.

Bovine respiratory syncytial virus (RSV) has substantial morbidity in young calves, and closely parallels human RSV in infants. We performed a randomized controlled trial in five to six-week-old Holstein calves (Bos taurus). comparing fusion protein inhibitor (FPI) and non-steroidal anti-inflammatory drug (NSAID) singly and in combination at three and five days after experimental BRSV infection. Thirty-six calves received one of six treatments; Ibuprofen started on day 3, Ibuprofen started on day 5, FPI started on day 5, FPI and Ibuprofen started on day 3, FPI and Ibuprofen started on day 5, or placebo. We have previously reported significant clinical benefits when combined FPI and NSAID treatment was started at three and five days after bovine RSV infection. Necropsy was performed on Day 10 following infection and hematoxylin and eosin staining was performed on sections from each lobe. Histology was described using a four-point scale. We performed canonical discrimination analysis (CDA) to determine the structural level where differences between treatments occurred and mixed effects regression to estimate effect sizes. Separation from placebo was maximal for dual therapy at the levels of the alveolus, septum, and bronchus in CDA. We found that the clinical benefits of combined FPI and NSAID treatment of BRSV extend at least partially from histopathological changes in the lung when treatment was started three days after infection. We found decreased lung injury when ibuprofen was started as monotherapy on day 3, but not day 5 following infection. Combined therapy with both an FPI and ibuprofen was always better than ibuprofen alone. We did not prove that the clinical benefits seen starting FPI and ibuprofen five days after infection can be solely explained by histopathological differences as identified on H&E staining.

BACKGROUND: Respiratory viral infections are a leading cause of disease worldwide. However, the overall community prevalence of infections has not been properly assessed, as standard surveillance is typically acquired passively among individuals seeking clinical care. METHODS: We conducted a prospective cohort study in which participants provided daily diaries and weekly nasopharyngeal specimens that were tested for respiratory viruses. These data were used to analyze healthcare seeking behavior, compared with cross-sectional ED data and NYC surveillance reports, and used to evaluate biases of medically attended ILI as signal for population respiratory disease and infection. RESULTS: The likelihood of seeking medical attention was virus-dependent: higher for influenza and metapneumovirus (19%-20%), lower for coronavirus and RSV (4%), and 71% of individuals with self-reported ILI did not seek care and half of medically attended symptomatic manifestations did not meet the criteria for ILI. Only 5% of cohort respiratory virus infections and 21% of influenza infections were medically attended and classifiable as ILI. We estimated 1 ILI event per person/year but multiple respiratory infections per year. CONCLUSION: Standard, healthcare-based respiratory surveillance has multiple limitations. Specifically, ILI is an incomplete metric for quantifying respiratory disease, viral respiratory infection, and influenza infection. The prevalence of respiratory viruses, as reported by standard, healthcare-based surveillance, is skewed toward viruses producing more severe symptoms. Active, longitudinal studies are a helpful supplement to standard surveillance, can improve understanding of the overall circulation and burden of respiratory viruses, and can aid development of more robust measures for controlling the spread of these pathogens.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalizations in young children. We estimated the burden of community-onset RSV-associated hospitalizations among US children aged <2 years by extrapolating rates of RSV-confirmed hospitalizations in 4 surveillance states and using probabilistic multipliers to adjust for ascertainment biases. METHODS: From October 2014 through April 2015, clinician-ordered RSV tests identified laboratory-confirmed RSV hospitalizations among children aged <2 years at 4 influenza hospitalization surveillance network sites. Surveillance populations were used to estimate age-specific rates of RSV-associated hospitalization, after adjusting for detection probabilities. We extrapolated these rates using US census data. RESULTS: We identified 1554 RSV-associated hospitalizations in children aged <2 years. Of these, 27% were admitted to an intensive care unit, 6% needed mechanical ventilation, and 5 died. Most cases (1047/1554; 67%) had no underlying condition. Adjusted age-specific RSV hospitalization rates per 100 000 population were 1970 (95% confidence interval [CI],1787 to 2177), 897 (95% CI, 761 to 1073), 531 (95% CI, 459 to 624), and 358 (95% CI, 317 to 405) for ages 0-2, 3-5, 6-11, and 12-23 months, respectively. Extrapolating to the US population, an estimated 49 509-59 867 community-onset RSV-associated hospitalizations among children aged <2 years occurred during the 2014-2015 season. CONCLUSIONS: Our findings highlight the importance of RSV as a cause of hospitalization, especially among children aged <2 months. Our approach to estimating RSV-related hospitalizations could be used to provide a US baseline for assessing the impact of future interventions.

IntroductionBovine respiratory syncytial virus (RSV) is a valid model for human RSV and an important bovine pathogen. Very early administration of ibuprofen and GS-561937, a fusion protein inhibitor (FPI), have separately been shown to decrease the severity of bovine RSV. Our aims were to determine how long after RSV inoculation ibuprofen and GS-561937 can be administered with clinical benefit and whether using both was better than monotherapy.Materials and methodsWe conducted a blinded randomized placebo controlled trial of ibuprofen, GS-561937 (FPI), or combinations of the two initiated at 3 or 5 days after artificial infection with bovine RSV in 36 five to six-week-old Holstein calves (Bos taurus). We measured clinical scores, respiratory rate, and viral shedding daily for 10 days following inoculation. We estimated the average effect for each drug and compared treatment arms using mixed effects models.ResultsWe found a significant decrease in clinical scores only in the combined treatment arms. This benefit was greater when treatment was initiated at 3 days rather than 5 days post infection with decreased clinical scores and lower respiratory rates at both time points. Ibuprofen alone started on day 3 increased, and FPI with ibuprofen started on day 3 decreased, viral shedding.ConclusionDual therapy with Ibuprofen and FPI, on average, decrease clinical severity of illness in a bovine model of RSV when started at 3 and 5 days after infection.

BACKGROUND Respiratory syncytial virus (RSV) is a common cause of severe respiratory illness in young children (< 5 years old) and older adults (≥ 65 years old) leading the World Health Organization (WHO) to recommend the implementation of a dedicated surveillance in countries. AIM We tested the capacity of the severe acute respiratory infection (SARI) hospital network to contribute to RSV surveillance in Belgium. METHODS During the 2018/19 influenza season, we started the SARI surveillance for influenza in Belgium in week 40, earlier than in the past, to follow RSV activity, which usually precedes influenza virus circulation. While the WHO SARI case definition for influenza normally used by the SARI hospital network was employed, flexibility over the fever criterion was allowed, so patients without fever but meeting the other case definition criteria could be included in the surveillance. RESULTS Between weeks 40 2018 and 2 2019, we received 508 samples from SARI patients. We found an overall RSV detection rate of 62.4% (317/508), with rates varying depending on the age group: 77.6% in children aged < 5 years (253/326) and 34.4% in adults aged ≥ 65 years (44/128). Over 90% of the RSV-positive samples also positive for another tested respiratory virus (80/85) were from children aged < 5 years. Differences were also noted between age groups for symptoms, comorbidities and complications. CONCLUSION With only marginal modifications in the case definition and the period of surveillance, the Belgian SARI network would be able to substantially contribute to RSV surveillance and burden evaluation in children and older adults, the two groups of particular interest for WHO.

IntroductionBovine respiratory syncytial virus (RSV) is a valid model for human RSV and an important bovine pathogen. Very early administration of ibuprofen and GS-561937, a fusion protein inhibitor (FPI), have separately been shown to decrease the severity of bovine RSV. Our aims were to determine how long after RSV inoculation ibuprofen and GS-561937 can be administered with clinical benefit and whether using both was better than monotherapy.Materials and methodsWe conducted a blinded randomized placebo controlled trial of ibuprofen, GS-561937 (FPI), or combinations of the two initiated at 3 or 5 days after artificial infection with bovine RSV in 36 five to six-week-old Holstein calves (Bos taurus). We measured clinical scores, respiratory rate, and viral shedding daily for 10 days following inoculation. We estimated the average effect for each drug and compared treatment arms using mixed effects models.ResultsWe found a significant decrease in clinical scores only in the combined treatment arms. This benefit was greater when treatment was initiated at 3 days rather than 5 days post infection with decreased clinical scores and lower respiratory rates at both time points. Ibuprofen alone started on day 3 increased, and FPI with ibuprofen started on day 3 decreased, viral shedding.ConclusionDual therapy with Ibuprofen and FPI, on average, decrease clinical severity of illness in a bovine model of RSV when started at 3 and 5 days after infection.

A key question for infectious disease dynamics is the impact of the climate on future burden. Here, we evaluate the climate drivers of respiratory syncytial virus (RSV), an important determinant of disease in young children. We combine a dataset of county-level observations from the US with state-level observations from Mexico, spanning much of the global range of climatological conditions. Using a combination of nonlinear epidemic models with statistical techniques, we find consistent patterns of climate drivers at a continental scale explaining latitudinal differences in the dynamics and timing of local epidemics. Strikingly, estimated effects of precipitation and humidity on transmission mirror prior results for influenza. We couple our model with projections for future climate, to show that temperature-driven increases to humidity may lead to a northward shift in the dynamic patterns observed and that the likelihood of severe outbreaks of RSV hinges on projections for extreme rainfall.

Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002–2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jcv.2015.08.014 Byline: Emilio E. Espinola, Graciela Russomando, Wilma Basualdo, Glaucia Paranhos-Baccala Author Affiliation: Departamento de Biologia Molecular y Biotecnologia, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion, Paraguay Hospital General Pediatrico Ninos de Acosta Nu, Ministerio de Salud Publica y Bienestar Social, Paraguay Emerging Pathogens Laboratory, Fondation Merieux, Lyon, France Article History: Received 4 May 2015; Accepted 27 August 2015.

Although respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in infants and adults at risk, no RSV vaccine is currently available. In this report, efforts toward the generation of an RSV subunit vaccine using recombinant RSV fusion protein (rRSV-F) are described. The recombinant protein was produced by transient gene expression (TGE) in suspension-adapted human embryonic kidney cells (HEK-293E) in 4 L orbitally shaken bioreactors. It was then purified and formulated in immunostimulating reconstituted influenza virosomes (IRIVs). The candidate vaccine induced anti-RSV-F neutralizing antibodies in mice, and challenge studies in cotton rats are ongoing. If successful in preclinical and clinical trials, this will be the first recombinant subunit vaccine produced by large-scale TGE in mammalian cells.

A key question for infectious disease dynamics is the impact of the climate on future burden. Here, we evaluate the climate drivers of respiratory syncytial virus (RSV), an important determinant of disease in young children. We combine a dataset of county-level observations from the US with state-level observations from Mexico, spanning much of the global range of climatological conditions. Using a combination of nonlinear epidemic models with statistical techniques, we find consistent patterns of climate drivers at a continental scale explaining latitudinal differences in the dynamics and timing of local epidemics. Strikingly, estimated effects of precipitation and humidity on transmission mirror prior results for influenza. We couple our model with projections for future climate, to show that temperature-driven increases to humidity may lead to a northward shift in the dynamic patterns observed and that the likelihood of severe outbreaks of RSV hinges on projections for extreme rainfall.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jcv.2015.08.014 Byline: Emilio E. Espinola, Graciela Russomando, Wilma Basualdo, Glaucia Paranhos-Baccala Author Affiliation: Departamento de Biologia Molecular y Biotecnologia, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion, Paraguay Hospital General Pediatrico Ninos de Acosta Nu, Ministerio de Salud Publica y Bienestar Social, Paraguay Emerging Pathogens Laboratory, Fondation Merieux, Lyon, France Article History: Received 4 May 2015; Accepted 27 August 2015.

Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002-2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.

Although respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in infants and adults at risk, no RSV vaccine is currently available. In this report, efforts toward the generation of an RSV subunit vaccine using recombinant RSV fusion protein (rRSV-F) are described. The recombinant protein was produced by transient gene expression (TGE) in suspension-adapted human embryonic kidney cells (HEK-293E) in 4 L orbitally shaken bioreactors. It was then purified and formulated in immunostimulating reconstituted influenza virosomes (IRIVs). The candidate vaccine induced anti-RSV-F neutralizing antibodies in mice, and challenge studies in cotton rats are ongoing. If successful in preclinical and clinical trials, this will be the first recombinant subunit vaccine produced by large-scale TGE in mammalian cells.

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV. However, no cross-neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well-characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus-specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross-neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross-neutralizing antibody and protective responses against more than one human pneumovirus.

BACKGROUND:Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in children less than 1 year of age in the United States. Internet search engine queries may provide high resolution temporal and spatial data to estimate and predict disease activity. METHODS:After filtering an initial list of 613 symptoms using high-resolution Bing search logs, we used Google Trends data between 2004 and 2016 for a smaller list of 50 terms to build predictive models of RSV incidence for five states where long-term surveillance data was available. We then used domain adaptation to model RSV incidence for the 45 remaining US states. RESULTS:Surveillance data sources (hospitalization and laboratory reports) were highly correlated, as were laboratory reports with search engine data. The four terms which were most often statistically significantly correlated as time series with the surveillance data in the five state models were RSV, flu, pneumonia, and bronchiolitis. Using our models, we tracked the spread of RSV by observing the time of peak use of the search term in different states. In general, the RSV peak moved from south-east (Florida) to the north-west US. CONCLUSIONS:Our study represents the first time that RSV has been tracked using Internet data results and highlights successful use of search filters and domain adaptation techniques, using data at multiple resolutions. Our approach may assist in identifying spread of both local and more widespread RSV transmission and may be applicable to other seasonal conditions where comprehensive epidemiological data is difficult to collect or obtain.

Respiratory syncytial virus (RSV) is associated with significant mortality rates amongst hematopoietic stem cell transplant (HSCT) recipients, with less known about other immunocompromised patients. Ten-year retrospective cohort study of immunocompromised patients presenting with RSV disease documented at University Hospitals of Lausanne and Geneva. Severe RSV-related outcomes referred to RSV documented respiratory conditions requiring hospital admission, presenting as lower respiratory tract infection (LRTI) or pneumonia. We used multivariable logistic regression to assess clinical and laboratory correlates of severe RSV disease. From 239 RSV-positive immunocompromised in and out-patients 175 were adults and 64 children of whom 111 (47.8%) presented with LRTI, which resulted in a 38% (89/239) admission rate to hospital. While immunocompromised children were more likely to be admitted to hospital compared to adults (75% vs 62.9%, p = 0.090), inpatients admitted to the intensive care unit (17/19) or those who died (11/11) were mainly adults. From multivariable analyses, adults with solid tumors (OR 5.2; 95% CI: 1.4-20.9 P = 0.015) or those requiring chronic immunosuppressive treatments mainly for rheumatologic conditions (OR 4.1; 95% CI: 1.1-16.0; P = 0.034) were significantly more likely to be admitted to hospital compared to hematopoietic stem cell (HSCT) recipients. Bacterial co-infection was significantly and consistently associated with viral LRTI and pneumonia. From our findings, RSV-related disease results in a significant burden among adults requiring chronic immunosuppressive treatments for rheumatological conditions and those with solid tumors. As such, systematic screening for respiratory viruses, should be extended to other immunocompromised populations than HSCT recipients.

BACKGROUND:Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in children less than 1 year of age in the United States. Internet search engine queries may provide high resolution temporal and spatial data to estimate and predict disease activity. METHODS:After filtering an initial list of 613 symptoms using high-resolution Bing search logs, we used Google Trends data between 2004 and 2016 for a smaller list of 50 terms to build predictive models of RSV incidence for five states where long-term surveillance data was available. We then used domain adaptation to model RSV incidence for the 45 remaining US states. RESULTS:Surveillance data sources (hospitalization and laboratory reports) were highly correlated, as were laboratory reports with search engine data. The four terms which were most often statistically significantly correlated as time series with the surveillance data in the five state models were RSV, flu, pneumonia, and bronchiolitis. Using our models, we tracked the spread of RSV by observing the time of peak use of the search term in different states. In general, the RSV peak moved from south-east (Florida) to the north-west US. CONCLUSIONS:Our study represents the first time that RSV has been tracked using Internet data results and highlights successful use of search filters and domain adaptation techniques, using data at multiple resolutions. Our approach may assist in identifying spread of both local and more widespread RSV transmission and may be applicable to other seasonal conditions where comprehensive epidemiological data is difficult to collect or obtain.

Maternal immunisation has the potential to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza, and pertussis immunisation during pregnancy has led to consideration of additional maternal immunisation strategies to prevent group B streptococcus and respiratory syncytial virus infections, among others. However, many gaps in knowledge regarding the immunobiology of maternal immunisation prevent the optimal design and application of this successful public health intervention. Therefore, we did an innovative landscape analysis to identify research priorities. Key topics were delineated through review of the published literature, consultation with vaccine developers and regulatory agencies, and a collaborative workshop that gathered experts across several maternal immunisation initiatives-group B streptococcus, respiratory syncytial virus, pertussis, and influenza. Finally, a global online survey prioritised the identified knowledge gaps on the basis of expert opinion about their importance and relevance. Here we present the results of this worldwide landscape analysis and discuss the identified research gaps.

Objective To determine the contribution of respiratory syncytial virus (RSV) to the subsequent development of severe asthma in different subgroups of children at risk of severe RSV disease. Settings The study was conducted in New South Wales (NSW), Australia. Participants The study comprised all children born in NSW between 2000 and 2010 with complete follow-up till 31 December 2011. The cohort was divided into three subgroups: (1) non-Indigenous high-risk children: non-Indigenous children born preterm or born with a low birth weight; (2) Indigenous children: children of mothers whose Indigenous status was recorded as Aboriginal and/or Torres Strait Islander and (3) non-Indigenous standard risk children: All other non-Indigenous term children. Primary outcome measure Risk of development of severe asthma in different subgroups of children who had RSV hospitalisation in the first 2 years of life compared with those who did not. Design We performed a retrospective cohort analysis using population-based linked administrative data. Extended Cox model was used to determine HR and 95% CI around the HR for first asthma hospitalisation in different subgroups of children. Results The cohort comprised 847 516 children born between 2000 and 2010. In the adjusted Cox model, the HR of first asthma hospitalisation was higher and comparable across all subgroups of children who had RSV hospitalisation compared with those who did not. The HR (95% CI) was highest in children aged 2-3 years; 4.3 (95% CI 3.8 to 4.9) for high-risk, 4.0 (95% CI 3.3 to 4.8) for Indigenous and 3.9 (95% CI 3.7 to 4.1) for non-Indigenous standard risk children. This risk persisted beyond 7 years of age. Conclusion This large study confirms a comparable increased risk of first asthma hospitalisation following RSV disease in the first 2 years of life across different subgroups children at risk.

Background Respiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children <5 years and associated financial impact on households in Bangladesh. Data of this study could be useful for RSV vaccine development and also the value of various preventive strategies, including use of an RSV vaccine in children if one becomes available. Methods From May through October 2010, children aged < 5 years with laboratory-confirmed RSV were identified from a sentinel influenza program database at four tertiary hospitals. Research assistants visited case-patients' homes after hospital discharge and administered a structured questionnaire to record direct medical costs (physician consultation fee, costs for hospital bed, medicines and diagnostic tests); non-medical costs (costs for food, lodging and transportation); indirect costs (caregivers' productivity loss), and coping strategies used by families to pay for treatment. We used WHO-Choice estimates for routine health care service costs. We added direct, indirect and health care service costs to calculate cost-per-episode of severe RSV illness. We used Monte Carlo simulation to estimate annual economic burden for severe RSV illness. Findings We interviewed caregivers of 39 persons hospitalized for RSV illness. The median direct cost for hospitalization was US$ 62 (interquartile range [IQR] = 43-101), indirect cost was US$ 19 (IQR = 11-29) and total cost was US$ 94 (IQR = 67-127). The median out-of-pocket cost was 24% of monthly household income of affected families (US$ 143), and > 50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV-associated hospitalization in children aged < 5 years in Bangladesh was US$ 10

Maternal immunisation has the potential to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza, and pertussis immunisation during pregnancy has led to consideration of additional maternal immunisation strategies to prevent group B streptococcus and respiratory syncytial virus infections, among others. However, many gaps in knowledge regarding the immunobiology of maternal immunisation prevent the optimal design and application of this successful public health intervention. Therefore, we did an innovative landscape analysis to identify research priorities. Key topics were delineated through review of the published literature, consultation with vaccine developers and regulatory agencies, and a collaborative workshop that gathered experts across several maternal immunisation initiatives-group B streptococcus, respiratory syncytial virus, pertussis, and influenza. Finally, a global online survey prioritised the identified knowledge gaps on the basis of expert opinion about their importance and relevance. Here we present the results of this worldwide landscape analysis and discuss the identified research gaps.

Background: Data on risk factors for respiratory syncytial virus (RSV)-associated hospitalisation in Australian children may be informative for preventive measures. Methods: A whole-of-population-based study was conducted to identify comparable risk factors for RSV hospitalisation in different subgroups of children aged <2 years in New South Wales. The cohort was divided into Indigenous children and high-risk and standard risk non-Indigenous children. Data on risk factors were obtained from the Perinatal Data Collection. RSV hospitalisations were ascertained from the Admitted Patient Data Collection. Adjusted HRs were calculated for each subgroup. Population-attributable risk associated with risk factors was estimated. Results: Four factors were associated with increased risk of RSV hospitalisation: maternal smoking during pregnancy, male sex, multiparity and birth during the first half of the RSV season. Increase in relative socioeconomic advantage was associated with decreased risk of hospitalisation. Among high and standard risk non-Indigenous children, the hazard was approximately double for children born to multiparous women compared to those born to primiparous women and among Indigenous children the hazard was approximately double among those born during the first half of the RSV season. Maternal smoking during pregnancy was associated with a 26-45% increased risk across subgroups and accounted for 17% (95% CI 9.3% to 24%) of RSV hospitalisations in Indigenous children, 5% (95% CI 2.5% to 8%) in high-risk and 6% (95% 5% to 7%) in standard risk non-Indigenous children. Discussion: Promoting avoidance of smoking during pregnancy may help in lowering the disease burden, with Indigenous children likely to benefit most.

BackgroundDespite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.MethodsWe prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.FindingsNPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively consi

Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for various conditions in cattle. Ibuprofen is an inexpensive short-acting NSAID and is readily available in liquid formulation for administration to bottle-fed calves. We compared the adverse effects of a 10-day course of ibuprofen and placebo in 16 five- to six-week-old Holstein bull calves that were being treated for experimentally induced bovine respiratory syncytial virus infection. Ibuprofen was administered as a liquid in milk replacer at 30 mg/kg divided three times daily. We found an increased prevalence of abomasal ulceration 5 of 8 in the ibuprofen compared to placebo group 2 of 6 (P = NS). There was one (1 of 8) case of mild interstitial nephritis in the ibuprofen and none (0 of 8) in the placebo group (P = NS). Renal function as measured by serum BUN and creatinine levels was not different between groups; no animal demonstrated an increase in creatinine.

BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated.AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children.METHODS: This was a population-based cohort study including data from 769,523 Danish children born between 1 January 1999 and 31 December 2010 and data from 581,742 Swedish children born between 1 July 2005 and 31 December 2010.RESULTS: Of the 1,351,265 children included, 1192 (0.09 %) were exposed to palivizumab. Nine cases of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80-2.95).CONCLUSION: The risk of autoimmune disease was not increased after palivizumab exposure. Given the small number of incident cases of autoimmune disease observed, this finding should be interpreted with caution.

Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood. In vivo studies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load. IMPORTANCE This study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.