871. Symptomatic Respiratory Syncytial Virus and Adenovirus Upper Respiratory Tract Infections Increase the Risk of Invasive Aspergillosis After Allogeneic Hematopoietic Cell Transplantation

Abstract Background Invasive aspergillosis (IA) is a serious infectious complication following hematopoietic cell transplantation (HCT). Few studies have reported respiratory viral infections (RVIs) as a risk factor for developing IA, and data regarding specific viruses is sparse. We examined whether specific respiratory viruses were associated with increased risk of developing IA post-HCT. Methods In a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted 2005–2010, weekly post-HCT nasal washes were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1 year post-HCT. Nasal and bronchoalveolar lavage (BAL) samples were tested by multiplex PCR for respiratory syncytial virus (RSV), parainfluenza viruses (PIV)1–4, influenza A/B, human metapneumovirus, adenovirus (ADV), and human rhinoviruses, and coronaviruses. Only respiratory virus detections with symptoms were counted as RVI. Separate Cox proportional hazards models were used to examine adjusted associations between each RVI and the development of first proven/probable IA by 1-year post-HCT. Results Among 437 patients who survived >28 days following HCT, 39 patients developed IA by 1-year post-HCT (median 87 days, range 5–283). After adjusting for age at HCT, neutropenia, high-grade CMV viremia, and HLA status (matched related vs. others) or severe acute graft-versus-host disease (GVHD Grade 0–2 vs. 3–4), RSV and ADV upper respiratory tract infections (URTI) were associated with increased risk of developing IA (figure). Detection of any respiratory virus in the BAL was associated with IA (P < 0.001). Conclusion RSV and ADV URTI are significant risk factors for development of IA post-HCT; the association between PIV URTI and development of IA approached statistical significance. Viral lower respiratory tract infection was associated with IA. Our data provide a rationale to assess IA as an endpoint in preventive studies of novel agents for respiratory viruses and further emphasize the importance of effective infection prevention practices for RVIs after HCT. Disclosures J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. A. Waghmare, Ablynx: Investigator, Research support. J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. M. Boeckh, Asun Biopharma: Consultant and Investigator, Consulting fee and Research support. Gilead Sciences: Consultant and Investigator, Consulting fee and Research support. Chimerix Inc.: Consultant and Investigator, Consulting fee and Research support. Humabs: Consultant, Consulting fee. GSK: Investigator, Research support.

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Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

BMC Infectious Diseases ◽

10.1186/s12879-021-05996-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Cheng Lei ◽

Lisong Yang ◽

Cheong Tat Lou ◽

Fan Yang ◽

Kin Ian SiTou ◽

...

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Pediatric Patients ◽

Respiratory Infections ◽

Upper Respiratory Tract ◽

Viral Etiology ◽

Upper Respiratory ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

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The Safety of Delayed Versus Immediate Antibiotic Prescribing for Upper Respiratory Tract Infections

Clinical Infectious Diseases ◽

10.1093/cid/ciaa890 ◽

2020 ◽

Cited By ~ 1

Author(s):

Tjeerd Pieter van Staa ◽

Victoria Palin ◽

Benjamin Brown ◽

William Welfare ◽

Yan Li ◽

...

Keyword(s):

Respiratory Tract ◽

Hospital Admission ◽

Respiratory Tract Infections ◽

Population Based ◽

Upper Respiratory Tract Infections ◽

Antibiotic Prescribing ◽

Upper Respiratory Tract ◽

Increased Risk ◽

Upper Respiratory ◽

Tract Infections

Abstract Background This study aimed to evaluate the clinical safety of delayed antibiotic prescribing for upper respiratory tract infections (URTIs), which is recommended in treatment guidelines for less severe cases. Methods Two population-based cohort studies used the English Clinical Practice Research Databank and Welsh Secure Anonymized Information Linkage, containing electronic health records from primary care linked to hospital admission records. Patients with URTI and prescriptions of amoxicillin, clarithromycin, doxycycline, erythromycin, or phenoxymethylpenicillin were identified. Patients were stratified according to delayed and immediate prescribing relative to URTI diagnosis. Outcome of interest was infection-related hospital admission after 30 days. Results The population included 1.82 million patients with an URTI and antibiotic prescription; 91.7% had an antibiotic at URTI diagnosis date (immediate) and 8.3% had URTI diagnosis in 1–30 days before (delayed). Delayed antibiotic prescribing was associated with a 52% increased risk of infection-related hospital admissions (adjusted hazard ratio, 1.52; 95% confidence interval, 1.43–1.62). The probability of delayed antibiotic prescribing was unrelated to predicted risks of hospital admission. Analyses of the number needed to harm showed considerable variability across different patient groups (median with delayed antibiotic prescribing, 1357; 2.5% percentile, 295; 97.5% percentile, 3366). Conclusions This is the first large population-based study examining the safety of delayed antibiotic prescribing. Waiting to treat URTI was associated with increased risk of hospital admission, although delayed antibiotic prescribing was used similarly between high- and low-risk patients. There is a need to better target delayed antibiotic prescribing to URTI patients with lower risks of complications.

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Antiviral and immunomodulatory effects of Engystol

Medical Council ◽

10.21518/2079-701x-2019-8-116-120 ◽

2019 ◽

pp. 116-120

Author(s):

R. A. Hanferian ◽

N. A. Daihes ◽

O. V. Karneeva ◽

T. I. Garashchenko ◽

I. A. Kim

Keyword(s):

Respiratory Tract ◽

Respiratory Tract Infections ◽

Symptomatic Treatment ◽

Infectious Agents ◽

Upper Respiratory Tract ◽

Immunomodulatory Effects ◽

Upper Respiratory ◽

Syncytial Virus ◽

Tract Infections ◽

Complex Drug

Respiratory tract infections are among the most common diseases. Most upper respiratory tract infections (URTI) are viral in nature. More than 200 types of viruses, including influenza, parainfluenza, respiratory syncytial virus (RSV), rhinovirus (HRV) and adenovirus (AV), may be the cause of URTI; in some cases, other infectious agents are the cause. The most common pathogens are rhinoviruses, which account for more than 50 per cent of the URTI. The article presents data on the efficacy of Engystol®, a complex drug containing low doses of active ingredients and used for prevention and symptomatic treatment of a number of viral diseases.

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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.

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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.

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