Respiratory Syncytial Virus Patients Research Articles

Clinical and epidemiological impact of respiratory syncytial virus and identification of risk factors for severe disease in children hospitalized due to acute respiratory tract infection.

Severe acute respiratory tract infection (ARTI) is a very common cause of hospitalization in pediatrics; respiratory syncytial virus (RSV) is the major etiologic agent. Accurately defining the burden of RSV life-threatening disease (LTD) and its risk factors is a challenge. To know the impact of RSV in children hospitalized due to ARTI and describe the risk factors for LTD. Prospective study in children < 2 years old hospitalized due to ARTI during 2012-2013 at Hospital de Niños "R. Gutiérrez." LTD was defined as requiring non-invasive ventilation and/or mechanical ventilation. 622 studied children, 372 were RSV(+) (59.8 %). Annual rate of hospitalization due to RSV in infants < 1 year old: 956 (95 % CI: 858-1062)/10 000hospitalizations. RSV caused 56/78 (71.8 %) cases of LTD; 42 (75 %) were previously healthy subjects; 32 (76.2 %) were < 6 months old. In the multivariate analysis, RSV was a risk factor for LTD (adjusted odds ratio [aOR]: 2.04; 95 % CI: 1.15-3.63; p = 0.014). A differential effect by sex was identified in RSV(+) patients: over-crowding was a risk factor for LTD in males (aOR: 2.36; 95 % CI: 1.07-5.21; p = 0.033); breastfeeding was a significant protective factor in females (aOR: 0.342; 95 % CI: 0.13-0.91; p = 0.032). RSV caused more than half of ARTI cases and mostly affected previously healthy patients < 1 year old. Males living in overcrowding conditions and females who were not breastfed were at the greatest risk for LTD.

PS1542 RESPIRATORY SYNCYTIAL VIRUS AND HUMAN METAPNEUMOVIRUS INFECTIONS AFTER ALLOGENEIC STEM CELL TRANSPLANTATION: IMPACT OF THE IMMUNODEFICIENCY SCORING INDEX AND RIBAVIRIN TREATMENT ON THE OUTCOMES

Background: Respiratory viral infections are a major cause of morbidity and mortality among allogeneic stem cell transplant recipients. In order to predict outcomes of the respiratory syncytial virus (RSV) infections in HSCT recipients, the immunodeficiency scoring index (ISI) was recently introduced. Aims: We decided to investigate the predictive role of the ISI in regards to progression to lower respiratory tract infection (LRTI) and mortality in an independent cohort of RSV and human metapneumovirus (hMPV) infected allogeneic stem cell transplant recipients. Methods: In total 71 patients were included in this study: 41 patients presented with upper respiratory tract infection (URTI) and 30 had primary LRTI. Patients were stratified as per ISI criteria into low, moderate and high-risk groups. Patients in the URTI cohort received treatment with either oral ribavirin (n = 20), intravenous ribavirin (n = 1) or with a combination of intravenous ribavirin and intravenous immunoglobulin (n = 1); 19 patients received no antiviral therapy. Patients in the LRTI cohort were treated either with intravenous ribavirin (n = 12), a combination of intravenous ribavirin and intravenous immunoglobulin (n = 16) or with oral ribavirin (n = 2). Results: Progression from URTI to LRTI was observed in 14% of the low-risk group, 20% of moderate and 75% of the high-risk group, p = 0,001. The trend of increased progression rate persisted after adjustment to received therapy, p < 0,0001. 21% of RSV-infected patients further progressed to LRTI compared to 29% of hMPV-infected patients, p = 0,524. In the LRTI cohort no (0%) virus-associated mortality was observed in the low-risk group compared to 16% in moderate and 43% in the high-risk group, p = 0,160. 17% deaths were observed among patients infected with RSV and 29% with hMPV, p = 0,517. With a median follow-up of 20 months, the median overall survival was not reached in both low and moderate-risk groups and was only 6 months in the high-risk group [95% CI: 0,23–11,77; p = 0,015]. Summary/Conclusion: ISI could predict progression from URTI to LRTI in a mixed cohort of RSV and hMPV infected allogeneic stem cell transplant recipients. The trend persisted after adjustment to received therapy. ISI was not able to predict mortality in the LRTI cohort but could predict overall survival in the entire cohort. No differences were observed in the outcomes of RSV and hMPV infected patients.

Dichloro-Phenyl-Benzotriazoles: A New Selective Class of Human Respiratory Syncytial Virus Entry Inhibitors.

Human Respiratory Syncytial Virus (RSV) is the primary cause of bronchopneumonia in infants and children worldwide. Clinical studies have shown that early treatments of RSV patients with ribavirin improve prognosis, even if the use of this drug is limited due to myelosuppression and toxicity effects. Furthermore, effective vaccines to prevent RSV infection are currently unavailable. Thus, the development of highly effective and specific antiviral drugs for pre-exposure prophylaxis and/or treatment of RSV infections is a compelling need. In the quest of new RSV inhibitors, in this work we evaluated the antiviral activity of a series of variously substituted 5,6-dichloro-1-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives in cell-based assays. Several 1- and 2-phenyl-benzotriazoles resulted fairly potent (μM concentrations) inhibitors of RSV infection in plaque reduction assays, accompanied by low cytotoxicity in human highly dividing T lymphoid-derived cells and primary cell lines. Contextually, no inhibitory effects were observed against other RNA or DNA viruses assayed, suggesting specific activity against RSV. Further results revealed that the lead compound 10d was active during the early phase of the RSV infection cycle. To understand whether 10d interfered with virus attachment to target cells or virus-cell fusion events, inhibitory activity tests against the RSV mutant strain B1 cp-52—expressing only the F envelope glycoprotein—and a plasmid-based reporter assay that quantifies the bioactivity of viral entry were also performed. The overall biological results, in conjunction with in silico modeling studies, supported the conclusion that the RSV fusion process could be the target of this new series of compounds.

Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in adults and a potential RSV vaccine for adults

BackgroundDeaths attributable to respiratory syncytial virus (RSV) among adults are estimated to exceed 11,000 annually, and annual adult hospitalizations for influenza and RSV may be comparable. RSV vaccines for older adults are in development. We assessed the following among primary care physicians (PCPs) who treat adults: (1) perception of RSV disease burden; (2) current RSV testing practices; and (3) anticipated barriers to adoption of an RSV vaccine. MethodsWe administered an Internet and mail survey from February to March 2017 to national networks of 930 PCPs. ResultsThe response rate was 67% (620/930). Forty-nine percent of respondents (n = 303) were excluded from analysis as they reported never or rarely caring for an adult patient with possible RSV in the past year. Among respondents who reported taking care of RSV patients (n = 317), 73% and 57% responded that in patients ≥ 50 years, influenza is generally more severe than RSV and that they rarely consider RSV as a potential pathogen, respectively. Most (61%) agreed that they do not test for RSV because there is no treatment. The most commonly reported anticipated barriers to a RSV vaccine were potential out-of-pocket expenses for patients if the vaccine is not covered by insurance (93%) and lack of reimbursement for vaccination (74%). ConclusionsPhysicians reported little experience with RSV disease in adults. They are generally not testing for it and the majority believe that influenza disease is more severe. Physicians will require more information about RSV disease burden in adults and the potential need for a vaccine in their adult patients.

118. Nasopharyngeal (NP) Bacterial Detection in Infants With Respiratory Syncytial Virus (RSV) Infection: Impact on Clinical Outcomes

BackgroundPrevious studies suggest that RSV increases NP bacterial colonization and may facilitate infection. However, the role of NP colonization with potentially pathogenic bacteria (PPB) in the pathogenesis of RSV bronchiolitis is not well understood. We sought to determine the frequency, type, and density of NP PPB detection in infants with RSV infection compared with healthy controls (HC), and its association with clinical outcomes.MethodsSingle-center, prospective study of previously healthy infants with RSV infection and age-matched HC. Inpatients (IP) were enrolled within 24 hours of hospitalization, outpatients (OP) at the ED or primary clinics and HC at well-child visits. RSV infection and the following PPB: [S. pneumoniae, M. catarrhalis, H. influenzae, and S. aureus] were detected and quantified by PCR. We compared demographic, clinical characteristics, and outcomes of care according to NP PPB detection.ResultsFrom 2010 to 2018, we enrolled 815 infants: 664 with RSV infection [IP, 560; OP, 104] and 151 HC. RSV+ OP (6.1 [3.7–10.7] months) and HC (6.9 [3.8–10.8] months) were older than IP (2.5 [1.4–5.4] months; P < 0.001). Identification of ≥1 PPB was 89% in RSV+ infants [IP, 88%; OP, 90%] versus 63% of HC (P < 0.0001). While H. influenzae or >1 PPB detection was higher in RSV infection (P < 0.001), S. aureus detection predominated in HC (P < 0.05; Figure 1). Frequency of S. pneumoniae detection was comparable between groups; however, S. pneumoniae loads were one log higher in RSV+ infants versus HC (P = 0.001) adjusted for antibiotic use. Differences in colonization rates remained different in RSV+ infants versus HC across age ranges (<3, 3–6, >6–12, and >12–24 months; Figure 2). Last, RSV patients (both IP and OP) with S. pneumoniae or H. influenzae detection had fever more frequently (70%–74% vs. 25%–47%; P < 0.0001), higher clinical disease severity scores (P = 0.01), and higher blood neutrophil counts (34%–36% vs. 16%–19%; P < 0.001), versus those with M. catarrhalis, S. aureus detection or PCR negative. In addition, NP detection of H. influenzae in RSV children was associated with higher frequency of atelectasis/consolidation by chest X-ray (P < 0.005).ConclusionThese data suggest that NP colonization with PPB is high in infants with RSV infection independent of age, and that specific bacteria, namely S. pneumoniae and H. influenzae, are associated with enhanced clinical disease severity. Disclosures A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support. O. Ramilo, Janssen Scientific Affairs, LLC: Consultant, Consulting fee. A. Mejias, Janssen: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Abbvie: CME talks, Speaker honorarium.

The Resource Burden of Infections With Rhinovirus/Enterovirus, Influenza, and Respiratory Syncytial Virus in Children.

We reviewed the resource utilization of patients with human rhinovirus/enterovirus (HRV/ENT), influenza A/B (FLU), or respiratory syncytial virus (RSV). A total of 2013 patients with nasopharyngeal swabs positive for HRV/ENT, RSV, or FLU were included. Records were reviewed for respiratory support, vascular access procedures, emergency department care only versus admission versus pediatric intensive care unit (PICU) care, antibiotics, length of stay, and billing data. Of the 2013 subjects, 1251 tested positive for HRV/ENT, 558 for RSV, and 204 for FLU. Fewer HRV/ENT patients were discharged from the emergency department ( P < .001); and they were more likely to be admitted to the pediatric intensive care unit ( P < .001). HRV/ENT and RSV patients were more likely to require invasive procedures ( P = .01). Median hospital costs for HRV/ENT patients were more than twice that of FLU patients ( P < .001). HRV/ENT infection in pediatric patients poses a significant resource and cost burden, even when compared with other organisms.

PIN129 - ADAPTING INFLUENZA PATIENT-REPORTED OUTCOMES (PRO) MEASURES TO MONITOR RESPIRATORY SYNCYTIAL VIRUS (RSV) SYMPTOM SEVERITY IN ADULTS: QUALITATIVE EVIDENCE OF KEY CONCEPTS AND CONTENT VALIDITY

Influenza virus and Respiratory Syncytial Virus (RSV) cause acute respiratory tract infections that present with similar symptoms. Although no PRO measures have been developed to monitor the severity of RSV symptoms in adults, influenza symptom PRO measures may be useful for RSV severity assessment. This study was conducted to evaluate the content validity of RSV adaptations of the FLU-PRO™ and Flu-iiQ™ (RI-PRO™ and R-iiQ™, respectively) for research in inpatients and outpatients with RSV infection. Combined concept elicitation and cognitive debriefing interviews were conducted with 28 US-English-speaking adults recently diagnosed with RSV (n=18) or influenza (n=10). Atlas.Ti was used for thematic analysis of verbatim transcripts. Similar symptoms were reported for RSV and influenza: ‘cough’, ‘wheezing’ and ‘fever’ were discussed by >75% of RSV and influenza patients. Some RSV patients (17%) also noted ‘rapid heartbeat’, ‘dry nose’, and ‘dry eyes.’ RSV patients understood both measures and confirmed both PROs assessed most ‘core’ RSV symptoms. The RI-PRO™ assessed more symptoms patients reported including ‘body/systemic’, ‘nasal’, ‘eye’ and ‘pain’ than the R-iiQ™, but not ‘wheezing.’ The R-iiQ™ symptom assessment was less comprehensive and some impact items were not relevant for inpatients. When symptoms were most severe, most RSV patients stated it would have been difficult for them to complete either measure. Robustly measuring RSV severity in adults is challenging. Content validity of RI-PRO™ and R-iiQ™ was supported, but neither measure provided the ideal assessment of symptoms for use in both inpatient/outpatient settings. Regulatory and best-practice guidelines highlight the need for a comprehensive symptom assessment to support content validity must be balanced with patient burden (e.g., brief symptom diaries) to monitor symptom severity daily or more often for severely ill hospitalized patients. This study identified symptoms most important to patients to include in a symptom diary for RSV inpatients and outpatients.

Healthcare resource use and economic burden attributable to respiratory syncytial virus in the United States: a claims database analysis

BackgroundDespite several studies that have estimated the economic impact of Respiratory Syncytial Virus (RSV) in infants, limited data are available on healthcare resource use and costs attributable to RSV across age groups. The aim of this study was to quantify age-specific RSV-related healthcare resource use and costs on the US healthcare system.MethodsThis retrospective case-control study identified patients aged ≥1 year with an RSV event in the Truven Health Marketscan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases between August 31, 2012 and August 1, 2013. RSV patients were matched 1:1 with non-RSV controls for age, gender, region, healthcare plan and index date (n = 11,432 in each group). Stratified analyses for healthcare resource use and costs were conducted by age groups. RSV-attributable resource use and costs were assessed based on the incremental differences between RSV cases and controls using multivariate analysis.ResultsRSV patients had a higher healthcare resource use (hospital stays, emergency room/urgent care visits, ambulatory visits and outpatient visits) than non-RSV matched controls for all age groups (all p < 0.0001), particularly in the elderly age groups with RSV (1.9 to 3 days length of stay, 0.4 to 0.5 more ER/UC visits, 0.7 to 2.7 more ambulatory visits, 12.1 to 18.6 more outpatient visits and 9.5 to 14.6 more prescriptions than elderly in the control groups). The incremental difference in adjusted mean annual costs between RSV and non-RSV controls was higher in elderly (≥65; $12,030 to $23,194) than in those aged < 65 years ($2251 to $5391). Among children, adjusted costs attributable to RSV were higher in children aged 5–17 years ($3192), than those 1–4 years ($2251 to $2521).ConclusionsOur findings showed a substantial annual RSV-attributable healthcare resource use and costs in the US across age groups, with the highest burden in those aged ≥65 years. These data can be used in cost-effectiveness analyses, and may be useful for policymakers to guide future RSV vaccination and other prevention programs.

Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses

BackgroundWhile almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA.ResultsViral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels.ConclusionsThe nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.

Risk of coronary artery lesions in young infants with Kawasaki disease: need for a new diagnostic method.

To examine clinical characteristics of Kawasaki disease (KD) in infants younger than 3 months of age and to develop a method for detecting KD in febrile infants. In a case-control study, we retrospectively collected clinical and laboratory data from 24 KD infants younger than 3 months of age out of 410 KD patients. We then compared younger infants with both older patients and febrile infants with respiratory syncytial virus (RSV) infection and urinary tract infections (UTI). The frequency of incomplete KD was higher in the younger group than in the control group (79% vs. 36%, P < 0.0001). Furthermore, before treatment, the incidence of coronary artery lesions (CAL) was significantly higher in the younger group (29% vs. 3.9%, P = 0.0001), resulting in a higher incidence of coronary artery sequelae (21% vs. 3.4%, P = 0.0023). Our results revealed that the serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level of KD patients was higher than that of RSV and UTI patients (3110 ± 2076 vs. 698 ± 436, P = 0.0001; and 971 ± 589 pg/mL, P = 0.0002, respectively). Thus, NT-proBNP might be suitable as a diagnostic marker of KD in young infants (P = 0.0005, criterion values: 1555 pg/mL [sensitivity: 80%, specificity: 85%]). Kawasaki disease infants younger than 3 months of age appear to be at higher risk for incomplete KD and early-onset CAL prior to the appearance of coronary artery sequelae. We suggest performing an echocardiogram and evaluating NT-proBNP in young infants with fever that has lasted longer than 2 days, regardless of the presence or absence of manifestations associated with KD.

Morbidity, and Short- and Intermediate-term Mortality, in Adults ≥60 Years Hospitalized with Respiratory Syncytial Virus Infection vs. Seasonal Influenza Virus Infection

Abstract Background There is increasing evidence that respiratory syncytial virus (RSV) infection can cause serious health problems among older adults, whether healthy and community-dwelling, or high-risk. In older adults, RSV infection can lead to complications that are similar to those resulting from seasonal influenza infection. The aim of this study was to compare the morbidity and mortality in older adults ≥60 years hospitalized with RSV disease vs. those hospitalized with seasonal influenza. Methods This cohort study included members of Kaiser Permanente Southern California aged ≥ 60 years who tested positive for RSV or influenza A/B by multiplex RT-PCR in clinical diagnostic testing during January 1, 2011 to June 30, 2015 and were hospitalized. For multiple eligible hospitalizations, only the first RSV hospitalization for the RSV cohort or first influenza A/B hospitalization for the influenza cohort was included. Electronic medical records for each hospitalized individual were used to extract necessary information, including baseline characteristics, symptoms, comorbidities, and outcomes. Results The study included 664 RSV (mean age 78.5 years, 39.5% male) and 1922 influenza A/B (mean age 77.5 years, 49.7% male) hospitalizations. There were 310 (46.7%) RSV patients and 501 (26.1%) influenza patients with a diagnosis of pneumonia. There were 119 RSV patients (17.9%) vs. 272 (14.2%) influenza patients that were admitted to the intensive care unit during hospitalization (mean stay 6.8 vs. 7.8 days). The short-term mortality rate during hospitalization and within 90 days of discharge was 5.6% (n = 37) and 7.4% (n = 49) in the RSV cohort vs. 4.4% (n = 85) and 6.7%&amp;#x2028;(n = 129) in the influenza cohort. The intermediate-term mortality rate within 91–180 days of discharge was significantly different between the RSV and the influenza cohorts (4.4% vs. 2.5%). Conclusion RSV infection can lead to complications and severe outcomes that are similar to those of seasonal influenza in older adults. Effective prevention and treatment strategies such as vaccination and antivirals against RSV could potentially reduce the burden of RSV infection as well as complications from disease. Disclosures H. F. Tseng, Novavax: Grant Investigator, Research grant. L. S. Sy, Novavax: Collaborator, Research grant. C. Fischetti, Novavax: Collaborator, Research grant. J. Slezak, Novavax: Collaborator, Grant recipient. Y. Luo, Novavax: Collaborator, Grant recipient. Z. Solano, Novavax Inc.: Collaborator, My employer received research funds to conduct the study. S. Chen, Novavax: Collaborator, Research grant. V. Shinde, Novavax Inc.: Collaborator, My employer received research funds to conduct the study.

Comparison of nasal cytokine profiles of human metapneumovirus and respiratory syncytial virus.

BackgroundHuman metapneumovirus (hMPV) and respiratory syncytial virus (RSV) share some epidemiological and clinical characteristics; however, few studies have examined the mechanisms by which these viruses induce airway inflammation.ObjectiveThis study was undertaken to compare cytokine profiles in hMPV and RSV patients to investigate possible differences in inflammatory pathways.MethodsNasopharyngeal aspirate specimens were collected from 1,008 pediatric patients hospitalized for acute lower respiratory tract infection with wheezing and 20 normal healthy controls. Patients were tested for 7 common respiratory viruses then divided into hMPV (n = 35) and RSV groups (n = 67). T helper (Th) 1 (interferon [IFN]-γ), Th2 (interleukin [IL]-4, eotaxin) and Th17 (IL-1β, IL-6) cytokine profiles were analyzed in the 3 groups.ResultsIFN-γ and IL-2 levels were significantly increased in the hMPV and RSV groups compared to the control group (p < 0.0001 and p < 0.0001, respectively). IL-4 levels were significantly higher in the RSV group compared to the hMPV and control groups (p = 0.0003 and p < 0.0001, respectively). Eotaxin levels showed a tendency to be higher in the RSV group compared to the hMPV group (p = 0.0580), and significantly higher compared to the control group (p < 0.0001). IL-1β levels were significantly higher in the hMPV compared to the RSV group (p < 0.0001), and IL-6 levels were significantly higher in the hMPV group compared to the control group (p < 0.0001).ConclusionOur results suggest that hMPV and RSV have different inflammatory mechanisms. hMPV induces airway inflammation by the Th17 pathway through release of IL-1β and IL-6, whereas RSV acts through the Th2 pathway.

A Virological and Phylogenetic Analysis of the Emergence of New Clades of Respiratory Syncytial Virus

The significant burden of Respiratory Syncytial Virus (RSV) in pediatric and elderly populations is well recognized. However, questions remain about transmission and evolution of RSV in the community, between seasons, and the role played by viral genetics in viral replication. Therefore, we integrated next generation sequencing, patient viral load, and viral replication analysis with surveillance of RSV to initiate a better understanding of viral adaptation in communities. RSV type-A and B infections were most closely related to RSV sequences from the USA and Asia, respectfully. The sample titres between RSV types-A and B were not significantly different. However, when the patient sample titre was compared to the phylogenetics of RSV, emergent clades were identified that we termed High Titre (HiT) clades of RSV. In conclusion, the correlation between patient viral load and replication kinetics of RSV patient isolates in culture indicated that viral genetics may determine virus replicative ability within patients. There was evolution or introduction of high-titre RSV type-A and B infections that seeded HiT clades in the subsequent year. Therefore, virological analysis of RSV isolates in conjunction with RSV phylogenetics may be a tool for predicting new clades of RSV in impending seasons.

Acute respiratory infections in hospitalized children in Vientiane, Lao PDR \u2013 the importance of Respiratory Syncytial Virus

The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children <5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD® kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children <3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time.

Characteristics of RSV-Specific Maternal Antibodies in Plasma of Hospitalized, Acute RSV Patients under Three Months of Age.

Respiratory syncytial virus (RSV) is the leading cause for respiratory illness that requires hospitalization in infancy. High levels of maternal antibodies can protect against RSV infection. However, RSV-infected infants can suffer from severe disease symptoms even in the presence of high levels of RSV-specific antibodies. This study analyzes several serological characteristics to explore potential deficiencies or surpluses of antibodies that could relate to severe disease symptoms. We compare serum antibodies from hospitalized patients who suffered severe symptoms as well as uninfected infants. Disease severity markers were oxygen therapy, tachypnea, oxygen saturation, admission to the intensive care unit and duration of hospitalization. Antibodies against RSV G protein and a prefusion F epitope correlated with in vitro neutralization. Avidity of RSV-specific IgG antibodies was lower in RSV-infected infants compared to uninfected controls. Severe disease symptoms were unrelated to RSV-specific IgG antibody titers, avidity of RSV-IgG, virus neutralization capacity or titers against pre- and postfusion F or G protein ectodomains and the prefusion F antigenic site Ø. In conclusion, the detailed serological characterization did not indicate dysfunctional or epitope-skewed composition of serum antibodies in hospitalized RSV-infected infants suffering from severe disease symptoms. It remains unclear, whether specific antibody fractions could diminish disease symptoms.

Retrospective Parameter Estimation and Forecast of Respiratory Syncytial Virus in the United States.

Recent studies have shown that systems combining mathematical modeling and Bayesian inference methods can be used to generate real-time forecasts of future infectious disease incidence. Here we develop such a system to study and forecast respiratory syncytial virus (RSV). RSV is the most common cause of acute lower respiratory infection and bronchiolitis. Advanced warning of the epidemic timing and volume of RSV patient surges has the potential to reduce well-documented delays of treatment in emergency departments. We use a susceptible-infectious-recovered (SIR) model in conjunction with an ensemble adjustment Kalman filter (EAKF) and ten years of regional U.S. specimen data provided by the Centers for Disease Control and Prevention. The data and EAKF are used to optimize the SIR model and i) estimate critical epidemiological parameters over the course of each outbreak and ii) generate retrospective forecasts. The basic reproductive number, R0, is estimated at 3.0 (standard deviation 0.6) across all seasons and locations. The peak magnitude of RSV outbreaks is forecast with nearly 70% accuracy (i.e. nearly 70% of forecasts within 25% of the actual peak), four weeks before the predicted peak. This work represents a first step in the development of a real-time RSV prediction system.

Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well‐defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty‐seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real‐time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged <1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness <14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co‐infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589–597, 2017 . © 2016 Wiley Periodicals, Inc.

Incidence of Hospitalization for Respiratory Syncytial Virus Infection amongst Children in Ontario, Canada: A Population-Based Study Using Validated Health Administrative Data.

ImportanceRSV is a common illness among young children that causes significant morbidity and health care costs.ObjectiveRoutinely collected health administrative data can be used to track disease incidence, explore risk factors and conduct health services research. Due to potential for misclassification bias, the accuracy of data-elements should be validated prior to use. The objectives of this study were to validate an algorithm to accurately identify pediatric cases of hospitalized respiratory syncytial virus (RSV) from within Ontario’s health administrative data, estimate annual incidence of hospitalization due to RSV and report the prevalence of major risk factors within hospitalized patients.Study Design and SettingA retrospective chart review was performed to establish a reference-standard cohort of children from the Ottawa region admitted to the Children’s Hospital of Eastern Ontario (CHEO) for RSV-related disease in 2010 and 2011. Chart review data was linked to Ontario’s administrative data and used to evaluate the diagnostic accuracy of algorithms of RSV-related ICD-10 codes within provincial hospitalization and emergency department databases. Age- and sex-standardized incidence was calculated over time, with trends in incidence assessed using Poisson regression.ResultsFrom a total of 1411 admissions, chart review identified 327 children hospitalized for laboratory confirmed RSV-related disease. Following linkage to administrative data and restriction to first admissions, there were 289 RSV patients in the reference-standard cohort. The best algorithm, based on hospitalization data, resulted in sensitivity 97.9% (95%CI: 95.5–99.2%), specificity 99.6% (95%CI: 98.2–99.8%), PPV 96.9% (95%CI: 94.2–98.6%), NPV 99.4% (95%CI: 99.4–99.9%). Incidence of hospitalized RSV in Ontario from 2005–2012 was 10.2 per 1000 children under 1 year and 4.8 per 1000 children aged 1 to 3 years. During the surveillance period, there was no identifiable increasing or decreasing linear trend in the incidence of hospitalized RSV, hospital length of stay and PICU admission rates. Among the Ontario RSV cohort, 16.3% had one or more major risk factors, with a decreasing trend observed over time.ConclusionChildren hospitalized for RSV-related disease can be accurately identified within population-based health administrative data. RSV is a major public health concern and incidence has not changed over time, suggesting a lack of progress in prevention.

Incidence, risk factors and hospital burden in children under five years of age hospitalised with respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) infections are among the most common lower respiratory tract infections in infants, but few studies have determined the age-specific incidence of hospitalisation in defined populations. This study gathered Swedish data on RSV in Gothenburg and its 10 surrounding municipalities from 2004 to 2011. Information was obtained from hospital databases of all patients up to five years of age who had a discharge diagnosis of an RSV infection and had a positive antigen detection or polymerase chain reaction test. A total of 1764 children fulfilled the inclusion criteria and 238 of these were preterm. The incidence under one year of age was 17.4/1000/year, and in children aged one to four years it was 0.6/1000/year. RSV patients occupied a mean of 1141 hospital beds per year: 65 were treated in the intensive care unit, 27 needed ventilator support, 19 needed continuous positive airway pressure, 408 (23%) received antibiotics, 399 (23%) received steroids, and all but four patients received a bronchodilator. All children survived. The incidence of RSV infections was high, medication use was high, and complications were low. Preterm infants had a higher risk, but most infants needing hospitalisation for RSV are full term and have no known risk factors.

Detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: Exacerbation versus stable condition.

Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.