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Expert Review of Anti-infective Therapy Apr 2017Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of... (Review)
Review
Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.
Topics: Acids, Carbocyclic; Amantadine; Antiviral Agents; Coronavirus Infections; Cyclopentanes; Guanidines; Humans; Immunocompromised Host; Influenza, Human; Oseltamivir; Palivizumab; Paramyxoviridae Infections; Picornaviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Ribavirin; Zanamivir
PubMed: 28067078
DOI: 10.1080/14787210.2017.1279970 -
Allergologia Et Immunopathologia 2015Infections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however, information about palivizumab efficacy in CF patients is almost lacking.
METHODS
A literature search up to December 2012 on the morbidity of RSV bronchiolitis in CF patients and on the safety and efficacy of palivizumab in those patients was performed. A random-effects meta-analysis was conducted for those studies meeting pre-specified search criteria. Historical controls were allowed.
RESULTS
The number of patients who received palivizumab was 354 and the hospital admission rate was 0.018 (95% CI 0.0077-0.048). The corresponding number in the non-treated groups was 463 patients with an admission rate of 0.126 (95% CI 0.086-0.182) (Q=13.9; p<0.001).
CONCLUSION
Palivizumab may have a role in the prevention of severe lower airway infection by RSV in CF patients.
Topics: Animals; Antiviral Agents; Cystic Fibrosis; Hospitalization; Humans; Palivizumab; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 24231153
DOI: 10.1016/j.aller.2013.09.003 -
Hospital Pediatrics Jun 2016The American Academy of Pediatrics recommends palivizumab prophylaxis against respiratory syncytial virus (RSV) for infants at high risk for severe disease within 72...
BACKGROUND
The American Academy of Pediatrics recommends palivizumab prophylaxis against respiratory syncytial virus (RSV) for infants at high risk for severe disease within 72 hours of hospital discharge to prevent community-associated RSV. The American Academy of Pediatrics does not recommend palivizumab to prevent health care-associated RSV (HA-RSV).
METHODS
A retrospective, multicenter cohort of hospitalized infants who received nondischarge palivizumab (NDP) between January 2009 and December 2013 was established from 14 hospitals. NDP was defined as a charge for palivizumab >7 days before hospital discharge and no previous documented RSV. Infants were considered high risk for severe disease if they had chronic lung disease, chronic heart disease, or prematurity. Nondischarge palivizumab use was examined for high- and low-risk infants. HA-RSV was defined as an RSV-positive test (polymerase chain reaction, enzyme immunoassays, or culture) >3 days after admission and the frequency was measured for infants who did and did not receive NDP.
RESULTS
We identified 1263 patients who received at least 1 dose of NDP, most of whom were classified as high risk (80%). Among high-risk patients, the predictors of receipt of NDP included longer length of stay, institution, and no comorbid conditions. Most of the low-risk patients (88%) who received NDP had no comorbid conditions. NDP use varied widely among institutions. Overall, 25 eligible patients developed HA-RSV; 17 of whom received NDP.
CONCLUSIONS
Despite current recommendations, palivizumab for prevention of HA-RSV was common, even among patients at low risk of severe RSV.
Topics: Antiviral Agents; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Inpatients; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Male; Palivizumab; Practice Guidelines as Topic; Respiratory Syncytial Virus Infections; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; United States
PubMed: 27164941
DOI: 10.1542/hpeds.2015-0238 -
Human Vaccines & Immunotherapeutics Dec 2024Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower...
Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK's Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity . These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV .
Topics: Infant; Animals; Humans; Infant, Newborn; Aged; Palivizumab; Nicotiana; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Antibodies, Viral; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Viral Fusion Proteins; Respiratory Syncytial Virus Vaccines; Mammals
PubMed: 38508690
DOI: 10.1080/21645515.2024.2327142 -
Vaccine Nov 2022Respiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal...
INTRODUCTION
Respiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal antibody available to protect infants from disease. A new and potentially longer-lasting monoclonal antibody, Nirsevimab, showed promising results in phase IIb/III trials. We evaluate the cost-effectiveness of Nirsevimab intervention programmes in England and Wales.
METHODS
We used a dynamic model for RSV transmission, calibrated to data from England and Wales. We considered a suite of potential Nirsevimab programmes, including administration to all neonates (year-round); only neonates born during the RSV season (seasonal); or neonates born during the RSV season plus infants less than six months old before the start of the RSV season (seasonal + catch-up).
RESULTS
If administered seasonally to all infants at birth, we found that Nirsevimab would have to be priced at £63 or less per dose for at least 50% certainty that it could cost-effectively replace the current Palivizumab programme, using an ICER threshold of £20,000/QALY. An extended seasonal programme which includes a pre-season catch-up becomes the optimal strategy at a purchasing price of £32/dose or less for at least 50% certainty. At a purchasing price per dose of £5-32, the annual implementation costs of a seasonal programme could be as high as £2 million before a switch to a year-round strategy would be optimal.
DISCUSSION
Nirsevimab has the potential to be cost-effective in England and Wales not only for use in high-risk infants.
Topics: Infant; Infant, Newborn; Humans; Respiratory Syncytial Virus Infections; Wales; Antiviral Agents; Palivizumab; Respiratory Syncytial Virus, Human; Antibodies, Monoclonal; England
PubMed: 36328884
DOI: 10.1016/j.vaccine.2022.10.041 -
The Pediatric Infectious Disease Journal Nov 2018Palivizumab provides passive immunity for respiratory syncytial virus (RSV), but poor adherence compromises protection. A hospital initiative promoted administration of...
BACKGROUND
Palivizumab provides passive immunity for respiratory syncytial virus (RSV), but poor adherence compromises protection. A hospital initiative promoted administration of first palivizumab doses at an outpatient clinic immediately after discharge. The objectives of this study were to evaluate the impact of the initiative on location and timing of first palivizumab dose, patient adherence, reimbursement, acquisition cost and RSV-positive hospital readmissions.
METHODS
This retrospective cohort study included pediatric patients who received palivizumab from 2012 to 2016. Three groups were compared: "before initiative," "transition" and "after initiative." Patients who did not qualify for palivizumab or who were eligible for palivizumab in previous RSV seasons were excluded. Multivariable logistic and linear regressions adjusted for patients' characteristics were used in outcome analysis.
RESULTS
After adjusting for patients' characteristics, there was a 13.5-fold (95% confidence interval: 5.9-30.5, P < 0.0001) increase in odds that patients would receive outpatient administration of palivizumab and 2.7-fold (95% confidence interval: 1.3-5.7, P = 0.0103) increase in odds of receiving the second dose within 35 days after initiative implementation compared with before. Although there was no significant difference in reimbursement percentage after initiative implementation (32% ± 30% after initiative and 31% ± 22% before), calculated palivizumab acquisition costs were 20.8% lower. RSV readmissions were not significantly different.
CONCLUSIONS
Implementation of an initiative with defined workflow, multidisciplinary collaboration, and early case management efforts to obtain insurance authorization increased outpatient administration of first palivizumab doses. Patient adherence improved as demonstrated by more timely receipt of the second palivizumab dose. There was no difference in reimbursement; however, acquisition cost decreased which is valuable considering low reimbursement rates. RSV-positive readmissions did not change significantly.
Topics: Ambulatory Care Facilities; Antiviral Agents; Drug Administration Schedule; Female; Hospitals; Humans; Infant; Insurance, Health, Reimbursement; Male; Medication Adherence; Palivizumab; Patient Discharge; Regression Analysis; Respiratory Syncytial Virus Infections; Retrospective Studies
PubMed: 29570593
DOI: 10.1097/INF.0000000000001999 -
Pediatrics Nov 2023
Topics: Humans; Palivizumab; Antiviral Agents; Vaccines
PubMed: 37682622
DOI: 10.1542/peds.2023-063817 -
Frontiers in Pharmacology 2020Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very...
OBJECTIVE
Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs.
DESIGN
Prospective animal study.
SETTING
Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia.
SUBJECTS
Four weaned Border-Leicester/Suffolk lambs at 5 months of age.
INTERVENTIONS
Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure.
MEASUREMENTS AND MAIN RESULTS
Both the HYDRA and AeroNeb Go produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 μm, range = 0.54-5.41μm) and the AeroNeb Go (3.07 ± 1.56 μm, range = 0.86-10 μm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung.
CONCLUSIONS
Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.
PubMed: 32973520
DOI: 10.3389/fphar.2020.01291 -
Human Vaccines & Immunotherapeutics Nov 2022Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab...
Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab was approved by the FDA in 1998 as RSV immunoprophylaxis to prevent severe RSV disease in children with specific health conditions and those born at <35 weeks gestational age (wGA). This study compared RSV-related hospitalization (RSVH) and RSVH characteristics in very preterm (<29 wGA) and term (>37 wGA) infants. Using the MarketScan Commercial and Multi-State Medicaid administrative claims databases, infants born between 7/1/2003 and 6/30/2020 were identified and classified as very preterm or term. Infants with evidence of health conditions, such as congenital heart disease and cystic fibrosis, were excluded. During 2003-2020 RSV seasons (November to March), claims incurred by infants while they were <12 months old were evaluated for outpatient administration of palivizumab and RSVH. The study included 40,123 very preterm infants and 4,421,942 term infants. Rate of RSVH in very preterm infants ranged 1.5-3.8 per 100 infant-seasons in commercially insured infants and 3.5-8.4 in Medicaid insured infants and were inversely related to wGA at birth. Relative risk of RSVH in very preterm was 3-4 times higher, and ICU admissions and mechanical ventilation were more common during RSVH in very preterm infants relative to term infants. However, these outcomes were less common or less severe in very preterm infants who received outpatient palivizumab administration, despite evidence of higher baseline risk of RSVH in these infants.
Topics: Infant; United States; Child; Infant, Newborn; Humans; Palivizumab; Gestational Age; Infant, Premature; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization; Infant, Premature, Diseases; Antiviral Agents
PubMed: 36412253
DOI: 10.1080/21645515.2022.2140533 -
The Pediatric Infectious Disease Journal Nov 2016Aboriginal infants are at risk for serious respiratory infection.
BACKGROUND
Aboriginal infants are at risk for serious respiratory infection.
OBJECTIVE
To determine the hazard rate (HR) for respiratory-related illness (RIH) and respiratory syncytial virus (RSV) specific infection hospitalization (RSVH) in Aboriginal versus non-Aboriginal children receiving palivizumab and the effect of adherence on hospitalization.
METHODS
Palivizumab recipients in the Canadian registry from 2005 to 2014 were included. Adherence was determined by the number of palivizumab doses received during the RSV season and interdose time interval. Adherence proportions between groups were compared by χ test. Cox proportional hazard analysis determined the effect of Aboriginal status and adherence on the risk of RIH and RSVH.
RESULTS
Aboriginal infants comprised 3.6% (701/19,235) of the registry. HR was 1.6 [95% confidence interval (CI): 1.3-2.0, P < 0.001] and 1.2 (95% CI: 0.7-2.2, P = 0.383) for RIH and RSVH. Aboriginal infants were 62.8% and 63.3% adherent with all recommended injections and within stipulated time intervals, respectively, whereas 81.9% (χ = 162.45, df = 1, P < 0.001) and 72.4% (χ = 27.35, df = 1, P = 0.002) of non-Aboriginal infants were correspondingly adherent. Only 39.9% of Aboriginals were perfectly adherent (adherent to total number and injection intervals), compared with 61.7% of non-Aboriginals (χ = 133.89, df = 1, P < 0.001). Even after adjustment for known risk factors, being Aboriginal and nonadherent was associated with higher RIH hazard (HR = 1.4, 95% CI: 1.1-1.8; HR = 1.3, 95% CI: 1.1-1.4, P = 0.004), respectively. Aboriginals nonadherent with interdose intervals had a 2.2-fold increased HR for RSVH (HR = 2.2, 95% CI: 1.2-4.2, P = 0.015).
CONCLUSIONS
Prophylaxed Aboriginal infants have a significantly increased RIH and RSVH hazard than non-Aboriginal infants. Improving adherence especially interdose frequency may further reduce hospitalizations in this vulnerable population.
Topics: Antiviral Agents; Canada; Female; Hospitalization; Humans; Infant; Inuit; Male; Medication Adherence; Palivizumab; Proportional Hazards Models; Respiratory Syncytial Virus Infections; Treatment Outcome
PubMed: 27331856
DOI: 10.1097/INF.0000000000001282