Low Sensitivity of BinaxNOW RSV in Infants

Abstract Background Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Early detection of RSV can optimize clinical management and minimize use of antibiotics. BinaxNOW RSV (BN) is a rapid antigen detection test that is widely used. We aimed to validate the sensitivity of BN in hospitalized and nonhospitalized infants against the gold standard of molecular diagnosis. Methods We evaluated the performance of BN in infants with acute respiratory tract infections with different degrees of disease severity. Diagnostic accuracy of BN test results were compared with molecular diagnosis as reference standard. Results One hundred sixty-two respiratory samples from 148 children from October 2017 to February 2019 were studied. Sixty-six (40.7%) samples tested positive for RSV (30 hospitalizations, 31 medically attended episodes not requiring hospitalization, and 5 nonmedically attended episodes). Five of these samples tested positive with BN, leading to an overall sensitivity of BN of 7.6% (95% confidence interval [CI], 3.3%–16.5%) and a specificity of 100% (95% CI, 96.2%–100%). Sensitivity was low in all subgroups. Conclusions We found a low sensitivity of BN for point-of-care detection of RSV infection. BinaxNOW RSV should be used and interpreted with caution.

Download Full-text

Therapeutic Antibodies for the Treatment of Respiratory Tract Infections—Current Overview and Perspectives

Vaccines ◽

10.3390/vaccines9020151 ◽

2021 ◽

Vol 9 (2) ◽

pp. 151

Author(s):

Alexie Mayor ◽

Adélaïde Chesnay ◽

Guillaume Desoubeaux ◽

David Ternant ◽

Nathalie Heuzé-Vourc’h ◽

...

Keyword(s):

Respiratory Tract Infections ◽

Inflammatory Diseases ◽

Treatment Strategies ◽

Candida Spp ◽

Medical Needs ◽

Life Threatening ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections ◽

Unmet Medical Needs

Respiratorytract infections (RTIs) are frequent and life-threatening diseases, accounting for several millions of deaths worldwide. RTIs implicate microorganisms, including viruses (influenza virus, coronavirus, respiratory syncytial virus (RSV)), bacteria (Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus and Bacillus anthracis) and fungi (Pneumocystis spp., Aspergillus spp. and very occasionally Candida spp.). The emergence of new pathogens, like the coronavirus SARS-CoV-2, and the substantial increase in drug resistance have highlighted the critical necessity to develop novel anti-infective molecules. In this context, antibodies (Abs) are becoming increasingly important in respiratory medicine and may fulfill the unmet medical needs of RTIs. However, development of Abs for treating infectious diseases is less advanced than for cancer and inflammatory diseases. Currently, only three Abs have been marketed for RTIs, namely, against pulmonary anthrax and RSV infection, while several clinical and preclinical studies are in progress. This article gives an overview of the advances in the use of Abs for the treatment of RTIs, based on the analysis of clinical studies in this field. It describes the Ab structure, function and pharmacokinetics, and discusses the opportunities offered by the various Ab formats, Ab engineering and co-treatment strategies. Including the most recent literature, it finally highlights the strengths, weaknesses and likely future trends of a novel anti-RTI Ab armamentarium.

Download Full-text

Reappraisal of respiratory syncytial virus as an aetiology of severe acute lower respiratory tract infections in children younger than 5 years in Nigeria

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz026 ◽

2019 ◽

Vol 113 (8) ◽

pp. 446-452

Author(s):

Damilola M Oladele ◽

Dimeji P Oladele ◽

Rasheedat M Ibraheem ◽

Mohammed B Abdulkadir ◽

Rasaki Adewole Raheem ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Preventive Strategy ◽

Lower Respiratory Tract Infections ◽

Cross Sectional ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

Download Full-text

Respiratory Syncytial Virus Infection Triggers Epithelial HMGB1 Release as a Damage-Associated Molecular Pattern Promoting a Monocytic Inflammatory Response

Journal of Virology ◽

10.1128/jvi.01279-16 ◽

2016 ◽

Vol 90 (21) ◽

pp. 9618-9631 ◽

Cited By ~ 33

Author(s):

Yashoda M. Hosakote ◽

Allan R. Brasier ◽

Antonella Casola ◽

Roberto P. Garofalo ◽

Alexander Kurosky

Keyword(s):

Epithelial Cells ◽

Respiratory Tract Infections ◽

Airway Disease ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Molecular Pattern ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infant and elderly populations worldwide. Currently, there is no efficacious vaccine or therapy available for RSV infection. The molecular mechanisms underlying RSV-induced acute airway disease and associated long-term consequences remain largely unknown; however, experimental evidence suggests that the lung inflammatory response plays a fundamental role in the outcome of RSV infection. High-mobility group box 1 (HMGB1) is a nuclear protein that triggers inflammation when released from activated immune or necrotic cells and drives the pathogenesis of various infectious agents. Although HMGB1 has been implicated in many inflammatory diseases, its role in RSV-induced airway inflammation has not been investigated. This study investigates the molecular mechanism of action of extracellularly released HMGB1 in airway epithelial cells (A549 and small airway epithelial cells) to establish its role in RSV infection. Immunofluorescence microscopy and Western blotting results showed that RSV infection of human airway epithelial cells induced a significant release of HMGB1 as a result of translocation of HMGB1 from the cell nuclei to the cytoplasm and subsequent release into the extracellular space. Treating RSV-infected A549 cells with antioxidants significantly inhibited RSV-induced HMGB1 extracellular release. Studies using recombinant HMGB1 triggered immune responses by activating primary human monocytes. Finally, HMGB1 released by airway epithelial cells due to RSV infection appears to function as a paracrine factor priming epithelial cells and monocytes to inflammatory stimuli in the airways.IMPORTANCERSV is a major cause of serious lower respiratory tract infections in young children and causes severe respiratory morbidity and mortality in the elderly. In addition, to date there is no effective treatment or vaccine available for RSV infection. The mechanisms responsible for RSV-induced acute airway disease and associated long-term consequences remain largely unknown. The oxidative stress response in the airways plays a major role in the pathogenesis of RSV. HMGB1 is a ubiquitous redox-sensitive multifunctional protein that serves as both a DNA regulatory protein and an extracellular cytokine signaling molecule that promotes airway inflammation as a damage-associated molecular pattern. This study investigated the mechanism of action of HMGB1 in RSV infection with the aim of identifying new inflammatory pathways at the molecular level that may be amenable to therapeutic interventions.

Download Full-text

Palivizumab e virus respiratorio sinciziale: una panoramica

Farmeconomia Health economics and therapeutic pathways ◽

10.7175/fe.v12i3s.984 ◽

2011 ◽

Vol 12 (3S) ◽

pp. 3-16

Author(s):

Paolo Manzoni

Keyword(s):

High Risk ◽

Respiratory Tract Infections ◽

Respiratory Infections ◽

Phase Iii ◽

Phase Iii Trials ◽

Risk Patients ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections ◽

Risk Categories

Respiratory Syncytial Virus (RSV) is a very frequent cause of respiratory infections in the first two years of life. Symptoms often are mild to moderate, but in some high-risk categories of infants, particularly prematures and children with bronchopulmonary dysplasia or congenital heart disease, RSV can cause severe lower respiratory tract infections with need of hospitalisation, and, sometimes, even death. No effective treatment is available, and specific vaccines, despite several attempts during the last decades, do not exist. Palivizumab is a humanised monoclonal antibody targeting specific viral mechanisms controlling infection. If administered intramuscularly monthly during the RSV season as prophylaxis to high risk patients < 2 years of age, this antibody effectively reduces hospitalisation rates and severity of RSV infection. Based on the data from the two main phase III trials conducted so far, palivizumab prophylaxis results in 45% to 55% reduction of hospitalisation rate, with a very satisfactory profile of tolerability as most commonly reported adverse events where transient and mild irritability, diarrhoea or fever.

Download Full-text

Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor

10.26434/chemrxiv.9894290.v1 ◽

2019 ◽

Author(s):

Victor Outlaw ◽

Jennifer T. Lemke ◽

Yun Zhu ◽

Samuel H. Gellman ◽

Matteo Porotto ◽

...

Keyword(s):

Viral Entry ◽

Respiratory Tract Infections ◽

Heptad Repeat ◽

Lower Respiratory Tract Infections ◽

Hydrophobic Contact ◽

Rsv Infection ◽

Dual Inhibitors ◽

Syncytial Virus ◽

Tract Infections ◽

Human Parainfluenza Virus

Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. There are currently no vaccines or antiviral therapeutics to treat existing HPIV3 or RSV infections. We recently reported a peptide (VIQKI), derived from the C-terminal heptad repeat (HRC) domain of the HPIV3 fusion (F) glycoprotein that inhibits infection by both HPIV3 and RSV. The dual inhibitory activity of VIQKI is due to its unique ability to bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F, thereby preventing the native HRN-HRC interactions required for viral entry. Here we describe the structure-guided design of dual inhibitors of HPIV3 and RSV fusion with improved efficacy. We show that VIQKI derivatives possessing one (I456F) or two (I454F/I456F) phenylalanine substitutions near the N-terminus exhibit more stable assemblies with RSV HRN domain and enhanced antiviral efficacy against both HPIV3 and RSV infection. Co-crystal structures of the new Phe-substituted inhibitors co-assembled with HPIV3 or RSV HRN domains reveal that the I456F substitution makes intimate hydrophobic contact with the core trimers of both HPIV3 and RSV F.

Download Full-text

738. Role of Respiratory Syncytial Virus and Mycoplasma pneumoniae in Pediatric Community-Acquired Lower Respiratory Tract Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.745 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S265-S265

Author(s):

Sanchit Kumar ◽

Anita Chakravarti ◽

Surinder Kumar ◽

Seema Kapoor

Keyword(s):

Respiratory Tract ◽

Predictive Value ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Rt Pcr ◽

Lower Respiratory Tract Infections ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Respiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood and Mycoplasma pneumoniae (M. pneumoniae) is a common cause of respiratory tract infections in all age groups. This study was conducted to determine the role of RSV and M. pneumoniae and in pediatric lower respiratory tract infections employing serological tests, polymerase chain reaction (PCR) and reverse transcriptase PCR analysis. Methods In this prospective study, 75 children aged 1 month to 5 years with acute lower respiratory tract infections (LRTIs) were investigated. Paired serum samples were obtained on admission and after 4–6 weeks to assay for M. pneumonia antibodies. Nasopharyngeal aspirates were obtained for the detection of RSV antigen by using the immunochromatographic test, reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and M. pneumoniae by PCR. Results RSV infection was positive in 20(60.60%) children aged <1 year and 13 (39.40%) aged 2–5 years, the difference being statistically insignificant (P = 0.360). M. pneumoniae infection was documented in a 15(57.6%) children aged <1 year age and 11(42.4%) in age 2–5 years which was statistically significant(P = 0.026). Clinical and radiological features among RSV and M. pnemoniae positive and negative cases were comparable. Thirty (40%) children were positive for RSV antigen and by RT-PCR and 3(12%) only by RT-PCR. Serological evidence of M pneumoniae infection was documented in 24(32%) children. M. pnemoniae PCR was positive in 8 (10.66%) patients. Together, serology and PCR detected M. pneumoniae in 26(34.66%) children. Considering RT-PCR as a diagnostic standard, the sensitivity of RSV antigen by immunochromatography was 90.90%, specificity 100%, positive predictive value 100% and a negative predictive value of 93.3%.The sensitivity of M. pneumoniae serology was 75%, specificity 73.3%, positive predictive value 25% and a negative predictive value of 96% considering PCR as a diagnostic standard,. Conclusion Our data underline the role of RSV and M. pneumoniae as the major cause of community-acquired lower respiratory tract infections in children aged <5 years. Disclosures All authors: No reported disclosures.

Download Full-text

Mean platelet volume as a diagnostic parameter of respiratory syncytial virus infection

Journal of Experimental and Clinical Medicine ◽

10.52142/omujecm.38.13 ◽

2021 ◽

Vol 38 (3) ◽

pp. 277-282

Author(s):

Hanife Hilal ANDAN ◽

Tugba TAS ◽

Güzide DOGAN ◽

Ayse Esra YILMAZ

Keyword(s):

Respiratory Tract ◽

Physical Examination ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Clinical Findings ◽

Lower Respiratory Tract Infections ◽

Positive Group ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections

Our aim was to investigate RSV related parameters by comparing clinical findings and physical examination with routinely ordered whole blood counts and biochemical variables in under two age children hospitalized for lower respiratory tract infections. The sample consisted of 193 children [RSV positive (n=85), RSV negative (n=108)] with lower respiratory tract infections from May 2010 to May 2013. Sociodemographic findings, chief complaints and physical examination findings were retrospectively evaluated. RSV positive and negative groups were compared using Chi-square test (% 95 Confidence Interval- %95 CI), Mann-Whitney U test (p:0,05). No significant differences were found in demographic variables and treatment decisions between two groups. In RSV positive group, higher hyponatremia (p ≤0.001) and AST values (p=0.003) were found. Decreased MPV were determined 71.8% in RSV positive group. RSV positive patients had decreased MPV values (OR:10.929, 95% CI). Higher hyponatremia and increased AST values were found to be associated with RSV infection; and decreased MPV was significantly related with RSV infection. This is the second study in literature within our knowledge that found decreased MPV values in RSV positive patients. The mechanism related with decreased MPV, hyponatremia, and increased AST values in RSV infection should be investigated further.

Download Full-text

Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor

10.26434/chemrxiv.9894290 ◽

2019 ◽

Author(s):

Victor Outlaw ◽

Jennifer T. Lemke ◽

Yun Zhu ◽

Samuel H. Gellman ◽

Matteo Porotto ◽

...

Keyword(s):

Viral Entry ◽

Respiratory Tract Infections ◽

Heptad Repeat ◽

Lower Respiratory Tract Infections ◽

Hydrophobic Contact ◽

Rsv Infection ◽

Dual Inhibitors ◽

Syncytial Virus ◽

Tract Infections ◽

Human Parainfluenza Virus

Download Full-text

Freesia Study Design: JNJ-53718678 in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

Blood ◽

10.1182/blood-2019-130423 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4478-4478 ◽

Cited By ~ 1

Author(s):

Roy Chemaly ◽

Michael Boeckh ◽

Karin Weber ◽

Roman Fleischhackl ◽

Marita Stevens ◽

...

Keyword(s):

Antiviral Activity ◽

Respiratory Tract ◽

Research Funding ◽

Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Rsv Infection ◽

Equity Ownership ◽

Upper Respiratory ◽

Syncytial Virus ◽

Tract Infections

Background Although Respiratory Syncytial Virus (RSV) is a commonly recognized respiratory pathogen that can cause upper respiratory tract infections (URTI) and severe lower respiratory tract infections (LRTI) in infants and young children, it can also affect immunocompromised (IC) patients. Hematopoietic cell transplantation (HCT) recipients are at high risk for severe disease caused by RSV. The progression of RSV from URTI to LRTI can cause significant morbidity, often leading to hospitalization, intensive care unit admissions for supportive care and results in mortality in 2-5% of RSV infected HCT recipients. At some clinical centers oral or intravenous ribavirin, intravenous immunoglobulin or anti-RSV-enriched antibody preparations are used to treat RSV infection. However, there are currently no approved direct-acting antiviral agents indicated for the prevention or treatment of RSV infection in IC adult patients. A recently conducted trial evaluating another RSV fusion inhibitor in HCT recipients demonstrated strong trends toward clinical benefit among patients who were early in their disease course and were severely immunocompromised. JNJ-53718678 (JNJ-8678) is a fusion protein inhibitor that was well tolerated and showed antiviral activity in a Phase 1b study of RSV-infected infants, and was well tolerated and demonstrated antiviral efficacy in healthy adult volunteers in a human viral challenge study. FREESIA will evaluate the clinical outcomes, antiviral activity, safety, tolerability, pharmacokinetics (PK), and PK/pharmacodynamics (PD) of JNJ-8678 in HCT recipients with RSV URTI who are at the highest risk for progression to LRTI. Study Design and Methods This is a randomized, double-blind, placebo-controlled, multi-center study to evaluate JNJ-8678 in adult and adolescent HCT recipients with RSV URTI. In the adult cohort, a sample size of approximately 249 patients is targeted. (Figure 1). Adult and adolescent HSCT recipients will be enrolled if they present for medical care with an absolute lymphocyte count <1,000 cells/μL, a PCR-based diagnosis of RSV infection, new onset of at least one respiratory symptom (nasal congestion, rhinorrhea, cough or pharyngitis) and/or worsening of one of these symptoms, if chronic due to an existing diagnosis, within 4 days prior to the anticipated start of dosing and no evidence of abnormalities consistent with LRTI on a chest X-ray. Eligible patients will be randomized 2:1 to receive orally either 500 mg JNJ-8678 once-daily (qd) or placebo qd for 21 days. The follow-up period will be 28 days in duration. The primary endpoint is the proportion of patients developing RSV LRTI, by external adjudication. Clinical course of RSV infection, antiviral activity, health-related quality of life, RSV viral sequencing and RSV viral kinetics will also be assessed. The PK/PD relationship of JNJ-8678 exposure with selected efficacy and safety parameters will be explored. Safety and tolerability, including AEs, laboratory assessments, ECGs, vital signs, and physical examination will be assessed. This study will begin recruitment globally in the northern hemisphere in November 2019. This study will clarify the role JNJ-8678 may play in the treatment of RSV in a broader IC population, potentially addressing a substantial unmet medical need. Disclosures Chemaly: Gilead: Research Funding; Gilead: Other: Personal fees; Chimerix: Research Funding; ReViral: Other: Personal fees; Oxford Immunotec: Other: Personal fees; Ansun: Other: Personal fees; Chimerix: Other: Personal fees; Oxford Immunotec: Research Funding; Merck: Research Funding; Ansun Pharmaceuticals: Research Funding; Janssen: Other: Personal fees; ADMA Biologics: Other: Personal fees; Merck: Other: Personal fees; Clinigen: Other: Personal fees; Ablynx: Other: Personal fees. Boeckh:Chimerix: Research Funding; GSK: Other: Personal fees; Merck: Research Funding; GSK: Research Funding; Clinigen: Other: Personal fees; Merck: Other: Personal fees. Weber:Janssen Pharmaceuticals: Employment; Johnson & Johnson: Equity Ownership. Fleischhackl:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Stevens:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Michiels:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Rivas:Janssen Pharmaceuticals: Employment; Johnson & Johnson: Equity Ownership. Chien:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Witek:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment.

Download Full-text

Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

Journal of Virology ◽

10.1128/jvi.79.10.6035-6042.2005 ◽

2005 ◽

Vol 79 (10) ◽

pp. 6035-6042 ◽

Cited By ~ 33

Author(s):

Negin Gitiban ◽

Joseph A. Jurcisek ◽

Randall H. Harris ◽

Sara E. Mertz ◽

Russell K. Durbin ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Upper Airway ◽

Upper Respiratory Tract ◽

Viral Pathogen ◽

Rsv Infection ◽

Upper Respiratory ◽

Syncytial Virus ◽

Tract Infections

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM.

Download Full-text