Red Book Recommendations on Ribavirin Challenged

PEDIATRICS ◽  
1994 ◽  
Vol 93 (5) ◽  
pp. 872-873
Author(s):  
Aaron R. Zucker
Keyword(s):  
Mechanical Ventilation ◽  
Critical Care ◽  
Respiratory Syncytial Virus ◽  
Lung Disease ◽  
University Of Chicago ◽  
Pediatric Critical Care ◽  
Mechanically Ventilated ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The University

I am the Director of Pediatric Critical Care at Wyler Children's Hospital at the University of Chicago. Because I had personally witnessed problems when administering ribavirin for respiratory syncytial virus (RSV) lung disease, I became interested in learning about others' experiences with the drug. At that time, no studies particular to the drug's use in mechanically ventilated infants had been published, yet the 1991 Red Book stated that "infants who require mechanical ventilation because of severe RSV infection are those who may be most likely to benefit from ribavirin treatment."

scholarly journals CD4+T Cells Drive Lung Disease Enhancement Induced by Immunization with Suboptimal Doses of Respiratory Syncytial Virus Fusion Protein in the Mouse Model

2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Kirsten Schneider-Ohrum ◽  
Angie Snell Bennett ◽  
Gaurav Manohar Rajani ◽  
Leigh Hostetler ◽  
Sean K. Maynard ◽  
...  
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Fusion Protein ◽  
Lung Disease ◽  
Rat Model ◽  
Preclinical Models ◽  
Cotton Rat ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTRespiratory syncytial virus (RSV) infection of seronegative children previously immunized with formalin-inactivated (FI) RSV has been associated with serious enhanced respiratory disease (ERD). The phenomenon was reproduced in the cotton rat and the mouse, and both preclinical models have been routinely used to evaluate the safety of new RSV vaccine candidates. More recently, we demonstrated that immunizations with suboptimal doses of the RSV fusion (F) antigen, in its post- or prefusion conformation, and in the presence of a Th1-biasing adjuvant, unexpectedly led to ERD in the cotton rat model. To assess if those observations are specific to the cotton rat and to elucidate the mechanism by which vaccination with low antigen doses can drive ERD post-RSV challenge, we evaluated RSV post-F antigen dose de-escalation in BALB/c mice in the presence of a Th1-biasing adjuvant. While decreasing antigen doses, we observed an increase in lung inflammation associated with an upregulation of proinflammatory cytokines. The amplitude of the lung histopathology was comparable to that of FI-RSV-induced ERD, confirming the observations made in the cotton rat. Importantly, depletion of CD4+T cells prior to viral challenge completely abrogated ERD, preventing proinflammatory cytokine upregulation and the infiltration of T cells, neutrophils, eosinophils, and macrophages into the lung. Overall, low-antigen-dose-induced ERD resembles FI-RSV-induced ERD, except that the former appears in the absence of detectable levels of viral replication and in the context of a Th1-biased immune response. Taken together, our observations reinforce the recent concept that vaccines developed for RSV-naïve individuals should be systematically tested under suboptimal dosing conditions.IMPORTANCERSV poses a significant health care burden and is the leading cause of serious lower-respiratory-tract infections in young children. A formalin-inactivated RSV vaccine developed in the 1960s not only showed a complete lack of efficacy against RSV infection but also induced severe lung disease enhancement in vaccinated children. Since then, establishing safety in preclinical models has been one of the major challenges to RSV vaccine development. We recently observed in the cotton rat model that suboptimal immunizations with RSV fusion protein could induce lung disease enhancement. In the present study, we extended suboptimal dosing evaluation to the mouse model. We confirmed the induction of lung disease enhancement by vaccinations with low antigen doses and dissected the associated immune mechanisms. Our results stress the need to evaluate suboptimal dosing for any new RSV vaccine candidate developed for seronegative infants.

scholarly journals Comparison of Intravenous Palivizumab and Standard of Care for Treatment of Respiratory Syncytial Virus Infection in Mechanically Ventilated Pediatric Patients

2016 ◽  
Vol 21 (2) ◽  
pp. 146-154 ◽  
Author(s):  
Brady J. Helmink ◽  
Carolyn E. Ragsdale ◽  
Evan J. Peterson ◽  
Kathryn G. Merkel
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Treatment Group ◽  
Length Of Stay ◽  
Pediatric Patients ◽  
Standard Of Care ◽  
Hospital Length Of Stay ◽  
End Points ◽  
Rsv Infection ◽  
Syncytial Virus

OBJECTIVES: Evidence suggests palivizumab may be beneficial for respiratory syncytial virus (RSV) infection in pediatric patients, although it is only approved by the US Food and Drug Administration for RSV prophylaxis. The objective of this study is to compare outcomes among pediatric patients with RSV infection who received intravenous palivizumab and standard of care versus standard of care alone. METHODS: This is a retrospective, single-center cohort study conducted between November 2003 and October 2013. Pediatric patients with active RSV infection treated with intravenous (IV) palivizumab after initiation of mechanical ventilation were matched 1:1 to a control selected from ventilated patients who received standard of care. The primary end point evaluated the duration of mechanical ventilation between groups. Secondary end points included hospital length of stay, intensive care unit length of stay, duration of respiratory support over baseline, time to RSV microbiologic cure, duration of antibiotic therapy, and in-hospital mortality. RESULTS: A total of 22 patients with a median age of 3 months were included in the study. Patients in the treatment group received a median of 2 doses of IV palivizumab, with a mean dose of 14.2 mg/kg. All patients received bronchodilators and corticosteroids, with the exception of 1 patient in the control group, and only 1 treatment group patient received IV ribavirin. Duration of mechanical ventilation was longer in the treatment group (18.9 ± 9.5 vs. 14.3 ± 9.3 days; p = 0.26). No statistically significant differences were observed between groups for any of the secondary end points. CONCLUSIONS: Pediatric patients who received IV palivizumab in addition to standard of care for treatment of RSV infection following initiation of mechanical ventilation experienced similar outcomes to those who received standard of care alone. Further studies are necessary to evaluate the potential benefit of IV palivizumab in addition to current standard of care.

scholarly journals A Case of Bilateral Spontaneous Chylothorax with Respiratory Syncytial Virus Bronchiolitis

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Mario Briceno-Medina ◽  
Michael Perez ◽  
Jie Zhang ◽  
Ronak Naik ◽  
Samir Shah ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Respiratory Syncytial Virus ◽  
Lung Disease ◽  
Congenital Heart ◽  
Septal Defect ◽  
Rsv Infection ◽  
History Of ◽  
Syncytial Virus ◽  
Rule Out

A case of bilateral spontaneous chylothorax with respiratory syncytial virus (RSV) bronchiolitis has never been reported. We report the case of a 7-month-old boy born at 33 weeks gestation with a history of Down syndrome, atrial septal defect, pulmonary hypertension, and chronic lung disease, hospitalized due to RSV bronchiolitis who developed bilateral spontaneous chylothorax with exacerbation of pulmonary hypertension (PH). The patient died after 9 weeks of mechanical ventilation and treatment for PH. The autopsy showed acute infectious signs, a chronic interstitial lung disease with pulmonary hypertensive changes and subpleural cysts with no evidence of congenital lymphangiectasia. The cause of chylothorax in this child could be multifactorial. However, worsening pulmonary hypertension with RSV infection might have partially contributed to the development of chylothorax through elevated superior venous cava pressure. Thoracentesis should be considered for patients with Down syndrome and PH associated with congenital heart disease who develop persistent pleural effusion during RSV bronchiolitis to rule out chylothorax.

Concerned About Ribavirin Recommendations

PEDIATRICS ◽  
1994 ◽  
Vol 94 (1) ◽  
pp. 132-133
Author(s):  
John F. Pope ◽  
James B. Besunder ◽  
Mary L. Kumar ◽  
Dennis M. Super
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Infectious Diseases ◽  
American Academy ◽  
Mechanically Ventilated ◽  
Mechanically Ventilated Patients ◽  
American Academy Of Pediatrics ◽  
Syncytial Virus ◽  
New Guidelines ◽  
Ventilated Patients

The Committee on Infectious Diseases of the American Academy of Pediatrics recently published new guidelines for using ribavirin in treating respiratory syncytial virus (RSV).1 In updating previous guidelines, the Committee, based on the study by Smith et al,2 added the recommendation that all RSV-infected patients who require mechanical ventilation should receive ribavirin. We believe the Committee's broad recommendation for using this drug in mechanically ventilated patients is premature. We have concerns about the Smith study that call into question their conclusions regarding the efficacy of ribavirin in mechanically ventilated children.

Severe Clinical Outcomes Among Adults Hospitalized With Respiratory Syncytial Virus Infections, New York City, 2017-2019

2021 ◽  
pp. 003335492110415
Author(s):  
Connor R. Goldman ◽  
William D. Sieling ◽  
Luis R. Alba ◽  
Raul A. Silverio Francisco ◽  
Celibell Y. Vargas ◽  
...  
Keyword(s):  
Older Adults ◽  
New York ◽  
Mechanical Ventilation ◽  
New York City ◽  
Risk Factor ◽  
Respiratory Syncytial Virus ◽  
York City ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Residential Living

Objectives Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. We assessed severe clinical outcomes among hospitalized adults that were associated with RSV infections. Methods We performed a nested retrospective study in 3 New York City hospitals during 2 respiratory viral seasons, October 2017–April 2018 and October 2018–April 2019, to determine the proportion of patients with laboratory-confirmed RSV infection who experienced severe outcomes defined as intensive care unit (ICU) admission, mechanical ventilation, and/or death. We assessed factors associated with these severe outcomes and explored the effect of RSV-associated hospitalizations on changes in the living situations of surviving patients. Results Of the 403 patients studied (median age, 69 years), 119 (29.5%) were aged ≥80. Severe outcomes occurred in 19.1% of patients, including ICU admissions (16.4%), mechanical ventilation (12.4%), and/or death (6.7%). Patients admitted from residential living facilities had a 4.43 times higher likelihood of severe RSV infection compared with patients who were living in the community with or without assistance from family or home health aides. At discharge, 56 (15.1%) patients required a higher level of care than at admission. Conclusions RSV infection was associated with severe outcomes in adults. Living in a residential facility at admission was a risk factor for severe outcomes and could be a proxy for frailty rather than an independent risk factor. Our data support the development of prevention strategies for RSV infection in older populations, especially older adults living in residential living facilities.

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

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