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Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF) lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa) acquisition, which is of particular importance in the youngest patients. We aimed to determine the effectiveness of PVZ on microbiological outcomes in young children with CF. We conducted a retrospective case-control study to compare these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not (PVZ-; n = 140). One case was matched with at least three same-gender controls born the same year and month. Median (range) age at first Pa isolation was not statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2-33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4 [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ- 41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not significantly differ between groups., Conclusion: Systematic PVZ use did not delay key pathogen acquisition in young children with CF. What is known: • Palivizumab is the only available monoclonal antibody against respiratory syncytial virus infection. • Whether or not it is useful in infants with cystic fibrosis remains controversial. What is new: • Palivizumab does not delay key pathogens (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children with cystic fibrosis. • Palivizumab does not reduce healthcare consumption or improve growth during the first 3 years of life of young children with cystic fibrosis.

Rationale: Respiratory syncytial virus (RSV) induces not only infantile recurrent wheezing but also potentially atopic asthma., Objectives: To test the effect of RSV infection on development of subsequent atopic asthma, we evaluated whether palivizumab, an anti-RSV monoclonal antibody, by preventing severe RSV disease in the first year of life, could impact subsequent recurrent wheezing and atopic asthma at 6 years of age., Methods: During the 2007 to 2008 RSV season, the decision to administer palivizumab was made based on standard medical practice and an observational prospective multicenter (n = 52) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed from 0 to 3 years (preceding Committee on Recurrent Wheezing study). The 52 investigators at hospitals then followed these subjects until 6 years of age, reported here (Effects of Preventive Treatment for Respiratory Syncytial [RS] Virus Infection During Infancy on Later Atopic Asthma in Preterm Infants; Scientific Committee for Elucidation of Infantile Asthma). Parents of study subjects reported the infants' physicians' assessment of recurrent wheezing, using a report card and a novel mobile phone-based reporting system using the Internet. The primary endpoint was the incidence of atopic asthma., Measurements and Main Results: Of 444 preterm infants enrolled, 349 received palivizumab during the first year of life. At 6 years, atopic asthma was not different in the groups: 15.3 and 18.2% of infants in the treated and untreated groups, respectively (P = 0.57). On the other hand, physician-diagnosed recurrent wheezing was observed in 15.3 and 31.6% in the treated and untreated groups, respectively (P = 0.003)., Conclusions: Palivizumab prophylaxis administered to preterm infants did not suppress the onset of atopic asthma but resulted in a significantly lower incidence of recurrent wheezing during the first 6 years. Clinical trial registered with www.clinicaltrials.gov (NCT 01545245).

Introduction: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants worldwide and also causes significant disease in the elderly. Despite 60 years of RSV research and vaccine development, there is only one approved medicine to prevent RSV infections. Palivizumab, a monoclonal antibody (mAb) against the RSV fusion (F) protein, is indicated for preterm infants and children at high-risk for RSV infections. It is an active time in RSV vaccine and mAb development with 14 vaccines and 2 mAbs currently being tested in clinical trials as of 13 February 2017. Active vaccination of women in the third trimester or passive immunization of infants with a mAb are particularly attractive approaches as the most severe disease occurs within the first 6 months of life. Areas covered: Here, we review current approaches for preventing RSV in the young and old, describe proposed clinical endpoints for studies in pediatric and adult clinical trials and highlight results from recent and ongoing clinical studies. Expert commentary: With 16 candidates in clinical development, approval of the first RSV vaccine or mAb for the prevention of RSV in all infants or the elderly is likely to occur in the next five years.

Bronchiolitis is among the most common illnesses in infants and children, and is the most common cause for hospitalization in infants in the U.S. This illness can be caused by many viruses, most commonly respiratory syncytial virus. It is diagnosed clinically by history and physical exam findings, with a narrow role for ancillary testing. Management is supportive, with medications demonstrating limited utility in multiple studies. Preventive measures include hand hygiene, breastfeeding, avoiding tobacco smoke exposure, and isolation precautions for hospitalized patients. Palivizumab prophylaxis is recommended for infants with qualifying high risk conditions. Recent evidence-based clinical practice guidelines have been published by the American Academy of Pediatrics to guide diagnosis, treatment, and prevention of bronchiolitis., (Copyright© South Dakota State Medical Association.)

Background: Infections with respiratory syncytial virus (RSV) are the leading cause for hospital admissions in infants and young children. The incidence of RSV-related hospitalizations in patients with cystic fibrosis (CF) is unclear. To date, no effective treatment for RSV infections is available. Thus, prophylaxis with the monoclonal antibody palivizumab is an important option., Methods: In a retrospective, single-center study at the Department of Pediatrics and Adolescent Medicine of the Medical University Graz, Austria, we analyzed all CF patients born between 1995 and 2012, who were admitted for respiratory problems between 1995 and 2014. We also defined a group of hypothetical RSV infections with the following criteria: admission caused by a respiratory infection during the first RSV season of life when no test for RSV was performed. Furthermore, we assessed the effectiveness of palivizumab as a prevention of RSV-related hospitalizations., Results: A total of 51 patients with CF were identified. The RSV-related hospitalization rate for the first RSV season was 0. Two patients (3.9%) were hospitalized 3 and 4 times, respectively, caused by RSV infections. The mean age at the time of admission was 12.4 ± 2.5 years. One case (1.9%) met our criteria for hypothetical RSV infections. There was no difference in RSV-related hospitalization rates between patients who received palivizumab and those who did not., Conclusions: We found a low rate of RSV-related hospitalizations and could not demonstrate a benefit of palivizumab prophylaxis regarding a decrease of RSV-related hospital admissions. The role of RSV reinfections in CF patients beyond infancy appears to be underestimated.

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. RSV was discovered more than 50 years ago, and despite extensive research to identify pharmacological therapies, the most effective management of this infection remains supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Currently, Palivizumab is the only available option for RSV prophylaxis, and because of restricted clinical benefits and high costs, it has been limited to a group of high-risk infants. There are several ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages for RSV vaccine development based on various strategies. Here we review the existing available prophylactic options, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is a common pathogen in infants with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection as the standard of care for infants with CF remains controversial., Objective: To evaluate the efficacy of palivizumab in reducing the incidence of RSV hospitalization in children with CF who are younger than 2 years., Methods: Four electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from inception until January 31, 2017, for clinical studies investigating the use of palivizumab in infants with CF aged less than 2 years. The primary outcome was hospitalization rate due to RSV infection. Secondary outcomes included hospitalization for respiratory illness, length of hospital stay, safety (adverse effects), and cost-effectiveness of palivizumab prophylaxis., Results: The review included a total of 10 studies (six cohort studies, two before-and-after studies, one cross-sectional study, and one randomized controlled trial) involving 3891 patients with CF. Seven studies reported that palivizumab prophylaxis had a positive impact on the rate of RSV hospitalization. Five studies (n=3404) reported that palivizumab prophylaxis significantly reduced the rate of hospitalization due to RSV infection compared to no prophylaxis. One study (n=5) demonstrated patients with CF who received palivizumab had no RSV hospitalization. Another study showed infants with CF receiving palivizumab (n=117) had a lower risk of hospitalization for RSV infection compared with premature infants (gestational age < 35 completed weeks) who received palivizumab (n=4880)., Conclusions: Evidence from the literature suggests that palivizumab may have a potential role in reducing RSV hospitalization in children aged less than 2 years with CF. Given the lack of overall data, additional research is warranted to better understand the efficacy and safety of prophylactic palivizumab in infants with CF., (© 2017 Pharmacotherapy Publications, Inc.)

Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897*, a highly potent human antibody, was optimized from antibody D25, which targets the prefusion conformation of the RSV fusion (F) protein. Crystallographic analysis of Fab in complex with RSV F from subtypes A and B reveals that MEDI8897* binds a highly conserved epitope. MEDI8897* neutralizes a diverse panel of RSV A and B strains with >50-fold higher activity than palivizumab. At similar serum concentrations, prophylactic administration of MEDI8897* was ninefold more potent than palivizumab at reducing pulmonary viral loads by >3 logs in cotton rats infected with either RSV A or B subtypes. MEDI8897 was generated by the introduction of triple amino acid substitutions (YTE) into the Fc domain of MEDI8897*, which led to more than threefold increased half-life in cynomolgus monkeys compared to non-YTE antibody. Considering the pharmacokinetics of palivizumab in infants, which necessitates five monthly doses for protection during an RSV season, the high potency and extended half-life of MEDI8897 support its development as a cost-effective option to protect all infants from RSV disease with once-per-RSV-season dosing in the clinic., (Copyright © 2017, American Association for the Advancement of Science.)

Background: Monthly injections of palivizumab during the respiratory syncytial virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations. However, the additive effect of naturally acquired immunity remains unclear. The objective of this study was to assess total neutralizing serum antibodies (NAb) against RSV in at-risk infants who had received an abbreviated course of palivizumab prophylaxis., Methods: Serum samples were collected from infants enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2 consecutive RSV seasons (2013 to 2015). Infants in this program had received an abbreviated course of palivizumab in accordance with the provincial guidelines. Data were compared to adults and infants less than 12 months of age who did not receive palivizumab. Anti-RSV NAb titers were measured using an RSV microneutralization assay., Findings: Infants who received palivizumab had anti-RSV NAb titers at the end of the RSV season that persisted beyond what is expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the control infants who did not receive palivizumab and all tested adults had protective anti-RSV NAb titers., Conclusions: Based on our observations, we hypothesize that naturally acquired NAb provide additive protection, which may significantly reduce the need for additional doses of palivizumab in infants at risk of severe RSV infections.

Objective: To obtain data on respiratory syncytial virus (RSV) associated hospitalization rates in preterm infants of 28 weeks gestational age and less in the era of palivizumab prophylaxis., Methods: Retrospective single-center cohort study including all preterm infants up to 28 weeks+6days gestational age and born between 2004 and 2012 at a tertiary care university hospital. Data on RSV related hospitalizations over the first two years of life covering at least two RSV seasons (November-April) were analyzed., Results: Ninety-one of 287 (32%) infants were hospitalized due to respiratory illness, and a total of 17 infants (5.9%) tested RSV positive during the first 2 years of life. Fourteen infants (4.9%) were hospitalized during the first RSV season. RSV hospitalization rate in infants with BPD was 4.5% (2/44) compared to 4.9% (12/243) without BPD. Palivizumab prophylaxis was documented in 74.6% of the infants. Infants with RSV compared to other respiratory tract infection were of younger age (6.8 vs. 9.1 months; p=0.049), had longer hospital stays (median 11 vs. 5 days; p=0.043) and more severe respiratory illness (median LRI score 3 vs. 2; p=0.043)., Conclusions: Despite palivizumab prophylaxis the burden of RSV disease and all cause respiratory illness was still remarkable in this vulnerable preterm population and mainly limited to the first season., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines., Methods: To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Children's Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses., Results: Among 3263 respiratory tract samples, 24.5% (798) and 37.3% (1216) were RSV and HRV positive, respectively. The odds of HRV infection were significantly lower in RSV-infected infants in all cohorts, with adjusted odds ratios of 0.30 (95% confidence interval [CI], .22-.40 in the INSPIRE study, 0.18 (95% CI, .11-.28) in the TCRI (adjusted for disease severity), and 0.34 (95% CI, .16-.72) in the MAKI trial. HRV infection was significantly more common among infants administered RSV immunoprophylaxis, compared with infants who did not receive immunoprophylaxis (OR, 1.65; 95% CI, 1.65-2.39)., Conclusions: A negative association of RSV on HRV codetection was consistently observed across populations, seasons, disease severity, and geographical regions. Suppressing RSV infection by RSV immunoprophylaxis might increase the risk of having HRV infection., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: 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.

Background: Children with cystic fibrosis (CF) are at higher risk of severe respiratory syncytial virus (RSV) infection, which can lead to a decline in lung function. A monoclonal antibody, palivizumab (PMB), effectively prevents RSV hospitalizations; however, the high cost of PMB, approximately C$10,000 per patient per RSV season, limits its widespread use. We assess the cost-effectiveness of PMB prophylaxis in CF children less than 2 y of age from the Canadian healthcare payer's perspective., Methods: In 2014, a Markov cohort model of CF disease and infant RSV infections in the Canadian setting was developed based on literature data. Infants were treated with monthly PMB injections over the 5-month RSV season. Lifetime health outcomes, quality-adjusted life years (QALYs) and 2013 $CAD costs, discounted at 5%, were estimated. Findings are summarized as incremental cost-effectiveness ratios (ICERs) and budget impact. Deterministic sensitivity analysis was conducted to assess parameter uncertainty., Results: Implementation of a hypothetical Canadian RSV prophylaxis program resulted in ICERs of C$652,560 (all CF infants) and C$157,332 (high-risk CF infants) per QALY gained and an annual budget impact of C$1,400,000 (all CF infants) and C$285,000 (high-risk CF infants). The analysis was highly sensitive to the probability of severe RSV, the degree of lung deterioration following infection, and the cost of PMB., Conclusions: Our results suggest PMB is not cost-effective in Canada by commonly used thresholds. However, given the rarity of CF and relatively small budget impact, consideration may be given for the selective use of PMB for immunoprophylaxis of RSV in high-risk CF infants on a case-by-case scenario basis.

Objective: The main objective was to evaluate the cost-effectiveness of protocol use of palivizumab in premature established by consensus in our Hospital comparing it based on the recommendations of various Scientific Societies. As a secondary objective risk factors and severity of hospitalized patients attending the established protocol in our Hospital were analyzed., Methods: The study period was 4 seasons with the expanded protocol (retrospective data) versus 2 with restricted or agreed protocol (prospective data). The perspective of the study was the Health System, including the costs of hospitalization and palivizumab our center. The calculation of the effectiveness was determined with the admission rate of premature patients stratified by weeks of gestational age &lt;29, &lt;32; and &lt;35. For the analysis of risk factors and severity in patients admitted seasons with the new protocol are collected prospectively clinical data and environmental and social factors., Results: In the range of gestational age &lt;29 years old and &lt;32 greater effectiveness of the extended protocol was not demonstrated against the consensus. Only more effective for EG &lt;35 in the accumulated data and comparing seasons 12/13 and 08/09 to 13/14 for individual data was observed. This range has an associated incremental cost effectiveness ratio of € 53 250,07 (range: € 14 793,39 to € 90 446,47 for singles data and € 50 525,53 (€ 28 688.22 to € 211 575,65) for accumulated. The establishment of this protocol in our center meant an average saving per season € 169 911,51. A cost-effectiveness of the extended protocol appropriate relationship is found if the cost of palivizumab per patient was less than € 1 206,67 (calculated for maximum use of the vial) and a higher rate of hospitalization of 9.21%. Children entering the season with the new protocol (season 12/13 and 13/14) are 63.4% in children under 3 months and 90% are term infants who do not belong to any population at risk, while many of them have associated risk factors you vary as have school-age siblings, rural residence, parental smoking, poor educational background of parents, lack of artificial feeding and family history of allergy., Conclusions: The consensus protocol has not been a significant increase in hospitalization rates in preterm infants &lt;32 weeks gestational age patients. In those &lt;35 has been observed a higher rate of hospitalization, with a very unfavorable cost-effectiveness for all clinical scenarios valued relationship., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Background: Respiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality., Objectives: To compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection., Patients/methods: In a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season., Results: The hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively., Conclusions: Infants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non-DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Children aged <2 years with chronic lung disease (CLD) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (RSVH) compared to healthy term infants. Based on the updated position statements, we compared respiratory-related illness hospitalization (RIH) and RSVH risks in CLD children who received palivizumab during the first year (FY) versus second year (SY) of life in the Canadian Registry of Palivizumab (CARESS). Demographic data were collected at enrolment and RIH events recorded monthly from 2005 to 2015. Eight hundred forty-seven FY and 450 SY children with CLD were identified. SY children had a lower gestational age (27 versus 29 weeks) and required more days of respiratory support (64 versus 43), oxygen therapy (108 versus 55), and length of stay (118 versus 73) during the neonatal course compared to FY children; all p < 0.0005. RIH rates were 12.2 (FY) and 18.2 (SY), and RSVH rates were 2.3 (FY) and 3.9 (SY). Cox regression showed similar hazards for both RIH (hazard ratio 0.9, 95% CI 0.6-1.6, p = 0.812) and RSVH (hazard ratio 1.1, 95% CI 0.4-2.9, p = 0.920)., Conclusions: SY and FY children had similar risks for RIH and RSVH. The findings imply that SY children with CLD are correctly selected for palivizumab based on neonatal illness severity and merit prophylaxis. What is Known: • Children with chronic lung disease have a 10-fold higher risk for RSV-positive hospitalization in comparison to healthy term infants and commonly receive palivizumab prophylaxis as a preventative measure against serious RSV-related lower respiratory tract infections. • The American Academy of Pediatrics [ 2 ] and the Canadian Paediatric Society [ 30 ] have recently modified their recommendations for RSV prophylaxis in children with chronic lung disease, limiting palivizumab to either those <32 weeks gestation or those in the first year of life who are oxygen dependent or require medical therapy for the treatment of their condition. What is New: • Children with chronic lung disease receiving an additional course of palivizumab in their second year of life were determined to be at similar risk for both respiratory illness-related hospitalization and RSV-positive hospitalization as palivizumab-naïve children enrolled in the first year of life in the Canadian Registry for palivizumab (CARESS). • CARESS physicians are correctly identifying high-risk children with chronic lung disease in their second year of life, whom they believe will benefit from an additional year of palivizumab prophylaxis, based on neonatal illness severity.

Objectives: To determine the differences in number of respiratory syncytial virus (RSV) hospitalizations and outcomes in infants 29 0/7 -34 6/7 weeks' gestational age (wGA) the season before (season 1 [S1]; 2013-2014) and after (season 2 [S2]; 2014-2015) implementation of the 2014 American Academy of Pediatrics revised guidance for palivizumab prophylaxis., Study Design: Children <12 months of age hospitalized with RSV infection were identified by the International Classification of Diseases, Ninth Revision codes and virology reports. Clinical, outcome data, palivizumab eligibility, and hospital charges were compared among infants 29-34 wGA in S1 vs S2., Results: Of 1063 RSV hospitalizations in infants <12 months old, 7.1% (34/482) in S1 and 9.8% (57/581) in S2 occurred in 29 0/7 -34 6/7 wGA infants. On the other hand, 29-34 wGA infants who were <6 months old constituted 3.5% (17/482) of RSV hospitalizations in S1 vs 7.1% (41/581) in S2 (P = .01). Among 29 0/7 -34 6/7 wGA healthy infants who were <3 months old, oxygen administration (40.0% vs 78.9%; P = .05), pediatric intensive care unit admission (30.0% vs 68.4%; P = .04), mechanical ventilation (10.0% vs 52.6%; P = .04), duration of hospitalization (1.8 vs 8.8 days; P = .04), and hospital charges ($19 686 vs $30 662; P = .03) significantly increased in S2 vs S1. No differences in morbidity were observed in premature infants who were 3 to <6 and 6 to <12 months between seasons. Palivizumab eligibility decreased from 32.3% in S1 to 1.8% in S2 (P < .001). One infant died in each season., Conclusions: In the year following implementation of the 2014 palivizumab prophylaxis guidance, there was an increase in RSV hospitalizations and associated morbidity among 29-34 wGA infants of younger chronological age., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (RSV) is the most common cause of this infection. RSV is transmitted through contact with respiratory droplets either directly from an infected person or self-inoculation by contaminated secretions on surfaces. Patients with RSV bronchiolitis usually present with two to four days of upper respiratory tract symptoms such as fever, rhinorrhea, and congestion, followed by lower respiratory tract symptoms such as increasing cough, wheezing, and increased respiratory effort. In 2014, the American Academy of Pediatrics updated its clinical practice guideline for diagnosis and management of RSV bronchiolitis to minimize unnecessary diagnostic testing and interventions. Bronchiolitis remains a clinical diagnosis, and diagnostic testing is not routinely recommended. Treatment of RSV infection is mainly supportive, and modalities such as bronchodilators, epinephrine, corticosteroids, hypertonic saline, and antibiotics are generally not useful. Evidence supports using supplemental oxygen to maintain adequate oxygen saturation; however, continuous pulse oximetry is no longer required. The other mainstay of therapy is intravenous or nasogastric administration of fluids for infants who cannot maintain their hydration status with oral fluid intake. Educating parents on reducing the risk of infection is one of the most important things a physician can do to help prevent RSV infection, especially early in life. Children at risk of severe lower respiratory tract infection should receive immunoprophylaxis with palivizumab, a humanized monoclonal antibody, in up to five monthly doses. Prophylaxis guidelines are restricted to infants born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease.

Background: Respiratory syncytial virus (RSV) infection frequently results in RSV-related hospitalization (RSVH) in young infants. We examined the outcomes of palivizumab recipients within the Canadian Registry (CARESS) and the Torino-Verona Italian Registry over the 2002-2014 RSV seasons., Methods: RSVHs were captured during the study seasons. Premature infants who received palivizumab (≤35 completed weeks' gestational age; group1) were compared with infants given palivizumab for underlying disorders regardless of gestational age (group 2). Variables and between-group incidences were analyzed. Risk factors associated with RSVH were assessed by logistic regression., Results: A total of 14,468 palivizumab-exposed infants were enrolled (group 1, n = 9093; group 2, n = 4856; miscellaneous, n = 519). RSVH was significantly more frequent in group 2 (211/4856, 4.34%) versus group 1 infants (216/9093, 2.37% [relative risk 1.93; 95% confidence interval (CI): 1.60-2.33; P < 0.0001]). Infants with neuromuscular disorders (7.88%), airway anomalies (5.95%), bronchopulmonary dysplasia (4.75%) and hemodynamically significant congenital heart disease (4.10%) had the highest RSVH incidences. After multivariable logistic regression, only neuromuscular disease [odds ratio [OR] 4.29; 95% CI: 2.30-8.00; P < 0.01], airway anomalies (OR 3.23; 95% CI: 1.92-5.43; P < 0.01), Down syndrome (OR 2.25; 95% CI: 1.31-3.89; P < 0.01), hemodynamically significant congenital heart disease (OR 2.24; 95% CI: 1.52-3.31; P < 0.001), prematurity ≤28 completed weeks' gestational age (OR 1.82; 95% CI: 1.29-2.58; P < 0.001) and bronchopulmonary dysplasia (OR 1.81; 95% CI: 1.31-2.50; P < 0.001) significantly predicted RSVH. No significant association was detected with the number of doses administered or the time elapsed after the previous dose., Conclusions: RSVH rates are higher in infants given palivizumab for reasons other than prematurity. It is uncertain whether these findings relate to inadequate current palivizumab dosing protocols or to a specific increased RSVH risk inherent in infants with severe underlying comorbidities.

Objective  SENTINEL1 characterized U.S. preterm infants 29 to 35 weeks' gestational age (wGA) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (RSV) disease and not receiving RSV immunoprophylaxis during the 2014 to 2015 RSV season. Study Design  This is a noninterventional, observational, cohort study. Results  A total of 702 infants were hospitalized with community-acquired RSV disease, of whom an estimated 42% were admitted to the intensive care unit (ICU) and 20% required invasive mechanical ventilation (IMV). Earlier gestational age and younger chronologic age were associated with an increased frequency of RSV-confirmed hospitalization (RSVH), ICU admission, and IMV. Among infants 29 to 32 wGA and < 3 months of age, 68% required ICU admission and 44% required IMV. One death occurred of an infant 29 wGA. Among the 212 infants enrolled for in-depth analysis of health care resource utilization, mean and median RSVH charges were $55,551 and $27,461, respectively, which varied by intensity of care required. Outpatient visits were common, with 63% and 62% of infants requiring visits before and within 1 month following the RSVH, respectively. Conclusion  Preterm infants 29 to 35 wGA are at high risk for severe RSV disease, which imposes a substantial health burden, particularly in the first months of life., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Vaccination of pediatric liver transplant candidates and recipients represents an opportunity to decrease infectious complications following transplant. Although vaccine recommendations exist, studies have shown that many transplant candidates and recipients are under-immunized. The goals of this study were to assess among pediatric transplant hepatologists: (i) current immunization practices before and after transplantation, (ii) involvement of an ID physician in the transplant evaluation, and (iii) perceptions about vaccine safety and barriers to immunization. An 80-item e-mail survey of pediatric transplant hepatologists at centers in the United States and Canada participating in the SPLIT consortium was conducted from December 2014 to March 2015. The overall response rate was 80% (73/91), representing 97% (32/33) of SPLIT centers. Fifty percent of programs routinely involved an ID physician in the transplant evaluation. Administration of palivizumab was routinely considered by 48% of hepatologists pre-transplant and by 41% post-transplant. Live vaccines were recommended by 26% of hepatologists after transplant. About 10% of hepatologists reported concern that live vaccines after transplant could induce rejection. There is wide variation in immunization practices among transplant hepatologists. Specific evidence-based protocols are needed to guide immunization practices in transplant candidates and recipients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Aims: To systematically review the effectiveness of preventative and therapeutic interventions for respiratory tract infections (RTIs) in people with Down's syndrome., Methods: Databases were searched for any published and ongoing studies of respiratory tract diseases in children and adults with Down's syndrome. These databases were searched for controlled trials, cohort studies and controlled before-after studies. Trial registries were searched for ongoing studies. Initially, all study types were included to provide a broad overview of the existing evidence base. However, those with a critical risk of bias were excluded using the Cochrane Risk of Bias tool., Results: A total of 13,575 records were identified from which 5 studies fulfilled the eligibility criteria and 3 fulfilled our criteria for data extraction. One randomized controlled trial of moderate risk of bias compared zinc therapy with placebo. Outcome data were only reported for 50 (78%) children who presented with extreme symptoms; no benefit of zinc therapy was found. One non-randomized controlled trial with serious risk of bias included 26 children and compared pidotimod (an immunostimulant) with no treatment; pidotimod was associated with fewer upper RTI recurrences compared with no treatment (1.43 vs. 3.82). A prospective cohort study with moderate risk of bias compared 532 palivizumab treated children with 233 untreated children and found that children treated with palivizumab had fewer respiratory syncytial virus-related hospitalization (23 untreated and 8 treated), but the same number of overall RTI-related hospitalizations (73 untreated and 74 treated) in the first 2 years of life., Conclusions: The evidence base for the management of RTIs in people with Down's syndrome is incomplete; current studies included children only and carry a moderate to serious risk of bias. Methodologic rigorous studies are warranted to guide clinicians in how best to prevent and treat RTIs in children with Down's syndrome., Competing Interests: We have read and understood the Pediatrics Infectious Diseases Journal policy on declaration of interests and declare that L.M. had financial support from the UK NIHR for the submitted work. There are no financial relationships with any organizations that may have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work exist. The authors have no conflicts of interest to disclose.

Respiratory syncytial virus (RSV) is a common cause of infection in immunocompromised patients and can lead to significant morbidity and mortality in pediatric hematopoietic stem cell transplantation (HSCT) patients and patients with a primary immune deficiency (PID). Palivizumab is a humanized monoclonal antibody that targets the F glycoprotein on the surface of the RSV virus, preventing RSV replication. Palivizumab was initially licensed for the prevention of RSV infections in children at high risk of severe disease. Since licensure, the American Academy of Pediatrics (AAP) has issued guidelines to help ensure appropriate use of palivizumab in pediatric patients. In the 2014 edition of the guidelines, the AAP recognizes that severe and fatal disease secondary to RSV can be seen in patients receiving chemotherapy or patients who are immunocompromised because of other conditions. However, they recognize that no large clinical trials exist to support the use of palivizumab, and efficacy and safety data in this population are limited. Despite this, the AAP recommends considering prophylaxis for children younger than 24 months who are profoundly immunocompromised during the RSV season. Because of the high cost of palivizumab, the uncertainty of its efficacy as prophylaxis in hospitalized pediatric HSCT and PID patients, and secondary to recent data from our center that suggested immunocompromised patients diagnosed with RSV did not have worse outcomes, we implemented very restrictive criteria for the use of palivizumab in the 2015 to 2016 RSV season in our pediatric HSCT population. Despite these strict criteria, there was no change in the number of patients developing RSV during this season compared with previous seasons, and there was no change in RSV course in those patients developing RSV compared with previous seasons. Restricted use also resulted in a significant dose and cost savings. Based on our experience, we recommend only administering prophylaxis palivizumab to the youngest and most high-risk HSCT patients during the RSV season., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Respiratory syncytial virus infection represents a clinical burden among young children under 24 months. Palivizumab is the only drug licensed in Italy for the prevention of serious lower respiratory tract disease requiring hospitalization caused by respiratory syncytial virus in children at high risk. However recommendations for palivizumab prophylaxis are heterogeneous. Not all the published documents agree about the clinical indications of palivizumab; this could lead to different clinical practices and concerns about the appropriateness of prophylaxis. These issues and the lack of evidence about palivizumab prophylaxis efficacy in specific medical conditions brought on the idea of a consensus conference on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications. The goal was to perform a review of the evidence regarding the efficacy and the safety of palivizumab and give recommendations in order to harmonize its use. A structured and validated method to conduct the consensus process was adopted. The consensus conference recommends palivizumab prophylaxis in infants born before 29 weeks and younger than 12 months at the start of the epidemic season. According to evidence from literature and experts' opinion, palivizumab prophylaxis is not recommended in preterm infants of gestational age ≥29 weeks, without co-morbidity (i.e., cardiac, bronchopulmonary diseases). The experts identified some clinical rare conditions for which the decision of prophylaxis should be entrusted to the specialists. The evaluation of the appropriateness of palivizumab prophylaxis in the single patient should be documented by the specialists. Pediatr Pulmonol. 2016;51:1088-1096. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Preterm/very low birth weight infants may suffer neurodevelopmental delays. Pediatricians should monitor neurodevelopment and pursue timely referrals. Yet parents who speak non-English primary languages (NEPL) report worse health care communication and fewer appropriate specialty referrals for their children. We sought to determine whether infants of NEPL parents receive recommended outpatient follow-up care for neurodevelopment. We hypothesized that these infants received less care than infants of English speakers., Methods: We linked paid claims from California Children's Services to clinical data from California Perinatal Quality Care Collaborative (58% linkage rate, 1541 subjects) for publicly insured infants with birth weight <1500 g or gestational age ≤32 weeks. Our primary outcomes were completion of 1) preventive visits and 2) ophthalmology visits; and receipt of 3) influenza vaccination and 4) palivizumab. To compare group differences, we also assessed 5) hospital length of stay and 6) readmissions. Analyses were adjusted for medical severity and sociodemographic characteristics., Results: A total of 433 infants (28%) had NEPL parents. Infants of NEPL parents had 38% higher odds of receiving influenza vaccination (95% confidence interval 9-75, P = .008) and completed 8% more preventive visits (95% confidence interval 1-64, P = .019) than infants of English speakers. Infants of NEPL parents did not have longer lengths of stay or more readmissions., Conclusions: Infants of NEPL parents were more likely than infants of English speakers to receive some aspects of recommended outpatient follow-up care. Regardless of language, all infants received far lower rates of follow-up care than recommended by national guidelines. Future study should address the causes of these gaps., (Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is a common reason for hospitalization of infants. In clinical trials, palivizumab reduced RSV hospitalization rates for premature infants. The 2014 American Academy of Pediatrics clinical practice guideline advised against use of palivizumab for otherwise healthy infants ≥29 weeks' gestation. The aim of this study was to determine the effect of palivizumab administration on hospitalization rates for RSV and bronchiolitis without RSV diagnosis among infants 29 to 36 weeks' gestation who do not have chronic illness., Methods: Claims data were extracted from databases of 9 Texas Medicaid managed care programs. Eligible infants were 29 to 36 weeks' gestation, without claims suggesting chronic illness, and who were born between April 1 and December 31 of 2012, 2013, and 2014., Results: A total of 2031 eligible infants of 29 to 32 weeks' gestation and 12 066 infants of 33 to 36 weeks' gestation were identified; 41.5% of the infants 29 to 32 weeks' gestation and 3.7% of the infants 33 to 36 weeks' gestation had paid claims for dispensing of ≥1 palivizumab doses. Among the infants of 29 to 32 weeks' gestation, palivizumab dispensing was associated with reduced RSV hospitalization rates (3.1% vs 5.0%, P = .04) but increased hospitalizations for bronchiolitis without RSV diagnosis (3.3% vs 1.9%, P = .05). There were no significant differences by palivizumab administration status for the infants of 33 to 36 weeks' gestation., Conclusions: Among infants 29 to 32 weeks' gestation without chronic illness, palivizumab use was associated with reduced RSV hospitalizations but increased hospitalizations for bronchiolitis without RSV diagnosis., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review., Objectives: To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016., Selection Criteria: Randomised and quasi-randomised studies., Data Collection and Analysis: The authors independently extracted data and assessed risk of bias., Main Results: One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio., Authors' Conclusions: We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.

Introduction: There is a lack of evidence concerning the effectiveness of immunoprophylaxis with palivizumab in children with childhood interstitial lung disease (chILD). In this retrospective study, we evaluated the effectiveness of palivizumab for decreasing the rate of RSV-related hospitalizations in children under the age of 24 months with chILD treated with corticosteroids., Methods: A retrospective national study was conducted in France. Patients born between 2007 and 2013, diagnosed with chILD and on corticosteroid treatment were identified through the French online database for pediatric interstitial lung disease (Respirare(®) ). Data were collected for the etiology and severity of chILD, risk factors and preventive measures for bronchiolitis, palivizumab immunoprophylaxis, and hospitalizations for bronchiolitis and RSV-bronchiolitis., Results: We included and evaluated 24 children during their first two RSV seasons, corresponding to 36 patient-seasons. The observed rate of RSV-related hospitalization (305/1000 patient-seasons), and the median length of stay (7 days), were higher than those for the general population. RSV-related hospitalization rates did not differ significantly between children with and without palivizumab prophylaxis (5/16 vs. 4/18, respectively, P = 0.70)., Conclusion: Children with chILD on corticosteroid treatment are at high risk of hospitalization for RSV-bronchiolitis, which tends to be more severe in these children than in the general population. The effectiveness of palivizumab prophylaxis in this population remains to be demonstrated. Pediatr Pulmonol. 2016;51:688-695. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: Data on risk factors for respiratory syncytial virus (RSV)-associated hospitalisation in Australian children may be informative for preventive measures., Methods: A whole-of-population-based study was conducted to identify comparable risk factors for RSV hospitalisation in different subgroups of children aged <2 years in New South Wales. The cohort was divided into Indigenous children and high-risk and standard risk non-Indigenous children. Data on risk factors were obtained from the Perinatal Data Collection. RSV hospitalisations were ascertained from the Admitted Patient Data Collection. Adjusted HRs were calculated for each subgroup. Population-attributable risk associated with risk factors was estimated., Results: Four factors were associated with increased risk of RSV hospitalisation: maternal smoking during pregnancy, male sex, multiparity and birth during the first half of the RSV season. Increase in relative socioeconomic advantage was associated with decreased risk of hospitalisation. Among high and standard risk non-Indigenous children, the hazard was approximately double for children born to multiparous women compared to those born to primiparous women and among Indigenous children the hazard was approximately double among those born during the first half of the RSV season. Maternal smoking during pregnancy was associated with a 26-45% increased risk across subgroups and accounted for 17% (95% CI 9.3% to 24%) of RSV hospitalisations in Indigenous children, 5% (95% CI 2.5% to 8%) in high-risk and 6% (95% 5% to 7%) in standard risk non-Indigenous children., Discussion: Promoting avoidance of smoking during pregnancy may help in lowering the disease burden, with Indigenous children likely to benefit most., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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., (Copyright © 2016 by the American Academy of Pediatrics.)

In July 2014, the Committee on Infectious Diseases (COID) updated their guidance on the use of palivizumab, recommending against use in preterm infants 29 to 35 weeks' gestational age (wGA). A primary data source cited to support this significant change was the low respiratory syncytial virus (RSV) hospitalization rate observed in the subpopulation of preterm (<37 wGA) infants evaluated from 2000 to 2005 through the New Vaccine Surveillance Network (NVSN). Here we critically appraise the preterm infant data from the NVSN in the context of data regarding the use of palivizumab in this same time period. Data from the NVSN, an analysis of Florida Medicaid data, and a national survey of US in-hospital palivizumab administration demonstrated that during 2001 to 2007, palivizumab was administered to 59% to 83% of preterm infants born at <32 wGA and 21% to 27% of all preterm infants (<37 wGA). When the NVSN data regarding incidence of RSV hospitalization in preterm infant subgroups were evaluated as a function of chronologic age, preterm infants <32 wGA showed a paradoxical increase in RSV hospitalization with older age, with the highest risk of RSV hospitalization occurring at 18 to 23 months of age. This pattern is most consistent with a reduction in RSV hospitalizations in <32 wGA infants in the first 12 to 18 months of life due to high palivizumab use at these young ages. The NVSN data were not designed to and cannot accurately describe RSV disease burden in preterm infants given the small size of the analyzed subpopulation and the high use of palivizumab during the study period.

Management of acute viral bronchiolitis is largely supportive. There is currently no proven effective therapy other than oxygen for hypoxic children. The evidence indicates that there is no routine benefit from inhaled, rapid short-acting bronchodilators, adrenaline or ipratropium bromide for children with acute viral bronchiolitis. Likewise, there is no demonstrated benefit from routine use of inhaled or oral corticosteroids, inhaled hypertonic saline nebulisation, montelukast or antibiotics. The last should be reserved for children with severe disease, when bacterial co-infection is suspected. Prevention of respiratory syncytial virus (RSV) disease remains a challenge. A specific RSV monoclonal antibody, palivizumab, administered as an intramuscular injection, is available for children at risk of severe bronchiolitis, including premature infants, young children with chronic lung disease, immunodeficiency, or haemodynamically significant congenital heart disease. Prophylaxis should be commenced at the start of the RSV season and given monthly during the season. The development of an RSV vaccine may offer a more effective alternative to prevent disease, for which the results of clinical trials are awaited. Education of parents or caregivers and healthcare workers about diagnostic and management strategies should include the following: bronchiolitis is caused by a virus; it is seasonal; it may start as an upper respiratory tract infection with low-grade fever; symptoms are cough and wheeze, often with fast breathing; antibiotics are generally not needed; and the condition is usually self limiting, although symptoms may occur for up to four weeks in some children.

Background: RSV causes considerable morbidity and mortality in children. In cystic fibrosis (CF) viral infections are associated with worsening respiratory symptoms and bacterial colonization. Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. Evidence regarding its effectiveness and safety in CF is inconclusive. CF screening in N. Ireland enabled timely palivizumab prophylaxis, becoming routine in 2002., Objectives: To determine the effect of palivizumab on RSV-related hospitalization and compare lung function and bacterial colonization at age 6 years for those born pre- and post-introduction of palivizumab prophylaxis., Methods: A retrospective audit was conducted for all patients diagnosed with CF during the period from 1997 to 2007 inclusive. RSV-related hospitalization, time to Pseudomonas aeruginosa (PA) 1st isolate, lung function and growth parameters were recorded. Comparisons were made for outcomes pre- and post-introduction of routine palivizumab administration in 2002. A cost evaluation was also performed., Results: Ninety-two children were included; 47 pre- and 45 post-palivizumab introduction. The overall RSV-positive hospitalization rate was 13%. The relative risk of RSV infection in palivizumab non-recipients versus recipients was 4.78 (95%CI: 1.1-20.7), P = 0.027. Notably, PA 1st isolate was significantly earlier in the palivizumab recipient cohort versus non-recipient cohort (median 57 vs. 96 months, P < 0.025) with a relative risk of 2.5. Chronic PA infection at 6 years remained low in both groups, with similar lung function and growth parameters. Total costs were calculated at £96,127 ($151,880) for the non-recipient cohort versus £137,954 ($217,967) for the recipient cohort., Conclusion: Palivizumab was effective in reducing RSV-related hospitalization infection in CF patients. Surprisingly, we found a significantly earlier time to 1st isolate of PA in palivizumab recipients which we could not explain by altered or improved diagnostic tests., (© 2016 Wiley Periodicals, Inc.)

Objective: To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010., Study Design: This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs)-acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications., Results: RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs-acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P < .001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV-associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country., Conclusions: The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: One hospital's implementation of revised American Academy of Pediatrics (AAP) guidelines for palivizumab prophylaxis of respiratory syncytial virus (RSV) infection is described., Methods: Revised AAP guidelines for RSV prophylaxis in infants and young children at increased risk for RSV infection recommend that up to five doses of palivizumab be administered during the RSV season. The guidelines also recommend that inpatients not receive monthly palivizumab prophylaxis and that infants and young children eligible for prophylaxis during the RSV season receive a dose of palivizumab two or three days before discharge or promptly after discharge. To ensure compliance with the revised AAP guidelines, a 296-bed hospital implemented a quality-improvement project including (1) efforts by the antimicrobial stewardship pharmacist and the chief medical officer to notify and educate healthcare providers regarding institutional adoption of the guidelines, (2) reinforcement of guideline adherence by clinical pharmacists during daily bedside rounds and via prospective review of all palivizumab orders, and (3) a medication-use evaluation (MUE) to assess adherence to the guidelines. The MUE results showed that during the 2014-15 RSV season (after implementation of the practice changes), the number of palivizumab doses administered at the hospital declined by 56% from the previous RSV season, with 97% of doses administered for appropriate indications., Conclusion: Standardized, comprehensive guidelines with defined criteria for palivizumab prophylaxis of RSV infection resulted in $303,227 of cost savings without a discernible change in nosocomial transmission, or morbidity, or mortality. Hospital infection-control practices controlled nosocomial RSV transmission., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Background: Palivizumab reduces the severity of respiratory syncytial virus infection in premature infants, but whether there is a protective effect beyond the preschool age is unknown. This study sought to assess the short- and long-term effects of palivizumab immunization on respiratory morbidity and pulmonary function at school age in children born extremely prematurely., Methods: Infants born before 29 weeks' gestation in 2000 to 2003 were assessed at school age by parental questionnaire, hospital chart review, and lung function tests. Children born immediately before the introduction of routine palivizumab prophylaxis were compared with age-matched children who received palivizumab prophylaxis during the first respiratory syncytial virus season., Results: Sixty-three children with a mean age 8.9 years were included: 30 had received palivizumab and 33 had not (control subjects). The groups were similar in terms of gestational age, birth weight, need for mechanical ventilation, and oxygen supplementation. Fifty-three percent of the palivizumab group, compared with 39% of the control group, had bronchopulmonary dysplasia (P = .14). Wheezing occurred in the first 2 years of life in 27% of the palivizumab group and in 70% of control subjects (P = .008); respective hospitalization rates were 33% and 70% (P = .001). At school age, rates of hyperresponsiveness (provocative concentration leading to a 20% fall in FEV1 < 1 mg/mL) were 33% and 48%, respectively (P = .38). Spirometry, lung volumes, diffusion, and exhaled nitric oxide were within normal limits, with no significant differences between groups., Conclusion: Palivizumab prophylaxis was associated with reduced wheezing episodes and hospitalizations during the first 2 years of life in children born extremely prematurely. However, it did not affect pulmonary outcome at school age., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Respiratory syncytial virus (RSV) is a predictable, seasonal disease with significant morbidity and mortality in children below 24 months. Prophylaxis, which decreases hospitalisation in those most vulnerable to the disease, has been available since 1998. Pharmacological prophylaxis is however, expensive and requires good infrastructure to deliver. It is out of reach for many patients in low-income and middle-income countries where mortality is highest. This article looks at the pathophysiology and risk factors for RSV. It also outlines what agents are currently available for prophylaxis and prevention., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

This recommendation updates the Argentinean Pediatrics' Neonatal Committee (CEFEN) ones published in 2007. The respiratory syncytial virus is the most frequent agent for lower respiratory infection. Tiny premature, bronchopulmonary dysplasia and significant hemodynamic congenital heart disease babies are the most vulnerable populations. Palivizumab is a humanized monoclonal antibody against respiratory syncytial virus used in the cold season. These recommendations are based on the scientific review of the literature published up to date. We reinforce the importance of general prevention measures like hand hygiene and family education among others. During the predominant season of respiratory syncytial virus in our country (April to September) a monthly dose of intramuscular 15 mg/kg of palivizumab is recommended. The safety and effectiveness has been proved as well as a reduction in the hospitalizations rates. In addition, epidemiological data of previous years are provided here., (Sociedad Argentina de Pediatría.)

Aim: To determine the incidence and outcomes of respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (ALRI) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (NICUs)., Methods: A multicenter, prospective study was conducted in newborns who were hospitalized with community acquired or nosocomial RSV infection in 44 NICUs throughout Turkey. Newborns with ALRI were screened for RSV infection by Respi-Strip®-test. Main outcome measures were the incidence of RSV-associated admissions in the NICUs and morbidity, mortality and epidemics results related to these admissions., Findings: The incidence of RSV infection was 1.24% (n: 250) and RSV infection constituted 19.6% of all ALRI hospitalizations, 226 newborns (90.4%) had community-acquired whereas 24 (9.6%) patients had nosocomial RSV infection in the NICUs. Of the 250 newborns, 171 (68.4%) were full-term infants, 183 (73.2%) had a BW >2500 g. RSV-related mortality rate was 1.2%. Four NICUs reported seven outbreaks on different months, which could be eliminated by palivizumab prophylaxis in one NICU., Conclusion: RSV-associated ALRI both in preterm and term infants accounts an important percent of hospitalizations in the season, and may threat other high-risk patients in the NICU.

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants. Palivizumab, a means of passive prophylaxis, relies on patient adherence to ensure therapeutic effectiveness. The objective of this study is to evaluate the association between adherence and the incidence of RSV-associated outcomes and to identify demographic factors that may impact adherence., Methods: Infants were recruited into the Canadian registry of palivizumab (CARESS) with parental consent. Monthly interviews collected information on palivizumab administration and RSV-associated outcomes. An infant was considered adherent if they received all of their expected injections or ≥5 injections within the appropriate interdose intervals., Results: Nineteen thousand two hundred thirty-five infants received a total of 83,447 injections from October 2005 to May 2014. Adherence was more likely in infants with higher maternal education and in those with siblings. Adherence was less likely in infants of aboriginal descent, with mothers who smoke and older infants. Adherence was significantly associated [odds ratio (95% confidence interval), P value] with a lower incidence of RSV infection [0.74 (0.60-0.93), 0.01] but not with RSV-associated hospitalization. However, in those hospitalized for RSV, adherence was significantly associated with the incidence of intubation and duration of hospitalization, intensive care stay and respiratory support., Conclusions: Adherence may have implications in children with less severe RSV infections and those who are already hospitalized for a RSV infection. Our study also identifies subpopulations that are more likely to be nonadherent to palivizumab therapy. Future studies should aim to validate the relationship among adherence, palivizumab levels and RSV-associated outcomes.

Background: Palivizumab prophylaxis for RSV has been consistently reported to reduce the risk of hospital admissions related to RSV infection in children with symptomatic cardiac disease. This study was designed to investigate the efficacy of palivizumab prophylaxis among infants with congenital heart disease (CHD) in Turkey., Methods: A total of 91 infants with CHD who received palivizumab prophylaxis and 96 infants with CHD without prophylaxis (0-12 months:52; 12-24 months:44) were included in this single-center retrospective case control study. Data on patient characteristics, household environment, and LRTIs were evaluated., Results: In patients without prophylaxis, the rate of overall lower respiratory tract infections (LRTIs) (P < 0.001), complicated LRTIs (P = 0.006), LRTI-related hospitalization (P < 0.001) and ICU admission (P = 0.008) were significantly higher than control patients. Weight <10th percentile (odds ratio (OR) 5.78, 95% confidence interval (CI):1.37; 24.4, P < 0.001) and concomitant chromosome abnormality (OR 4.01, 95% CI:1.01;16.45, P < 0.001) in patients with prophylaxis, while presence of a sibling <11 years of age (OR 3.38, 95% CI: 1.21; 9.46, P < 0.001) and congestive heart failure (OR 8.63, 95% CI: 2.81; 26.6, P < 0.001) in the control group were the significant correlates of LRTI-related hospitalization., Conclusion: Our findings revealed significantly lower rate of overall and complicated LRTIs, LRTI-related hospitalization and ICU admissions in infants with CHD via palivizumab prophylaxis., (© 2014 Wiley Periodicals, Inc.)

This study was done to evaluate respiratory syncytial virus (RSV) related readmission (RRR) and risk factors of RRR in preterm infants < 34 weeks gestational age (GA) within 1 yr following discharge from the neonatal intensive care unit (NICU). Infants (n = 1,140) who were born and admitted to the NICUs of 46 hospitals in Korea from April to September 2012, and followed up for > 1 yr after discharge from the NICU, were enrolled. The average GA and birth weight of the infants was 30(+5) ± 2(+5) weeks and 1,502 ± 474 g, respectively. The RRR rate of enrolled infants was 8.4% (96/1,140), and RSV accounted for 58.2% of respiratory readmissions of infants who had laboratory tests confirming etiological viruses. Living with elder siblings (odd ratio [OR], 2.68; 95% confidence interval [CI], 1.68-4.28; P < 0.001), and bronchopulmonary dysplasia (BPD) (OR, 2.95; 95% CI, 1.44-6.04; P = 0.003, BPD vs. none) increased the risk of RRR. Palivizumab prophylaxis (OR, 0.06; 95% CI, 0.03-0.13; P < 0.001) decreased the risk of RRR. The risk of RRR of infants of 32-33 weeks' gestation was lower than that of infants < 26 weeks' gestation (OR, 0.11; 95% CI, 0.02-0.53; P = 0.006). This was a nationwide study that evaluated the rate and associated risk factors of RRR in Korean preterm infants. Preterm infants with BPD or living with siblings should be supervised, and administration of palivizumab to prevent RRR should be considered.

In 2014, the American Academy of Pediatrics (AAP) updated their recommendations for palivizumab prophylaxis for children who are at high risk for severe respiratory syncytial virus (RSV) infection. To investigate the potential impact of the more restrictive 2014 criteria on the eligibility for palivizumab prophylaxis, we applied the 2012 and 2014 AAP recommendations for palivizumab prophylaxis to a multicenter cohort of 2207 US children hospitalized for bronchiolitis. According to the 2012 AAP recommendations, 215 children (9.7%) were eligible for palivizumab prophylaxis, while 140 children (6.3%) would have been eligible based on the 2014 updated recommendations (34.9% relative decrease; 95%CI: 28.5-41.7%). The decrease was largely driven by the restriction of eligibility to preterm infants with gestational age <29 weeks. Further development of and refinement of cost-effective approaches for the prevention of severe RSV infection are needed., (© 2015 Japan Pediatric Society.)

Objective: This study aims to determine predischarge palivizumab receipt prevalence among infants ≤ 36 weeks' gestational age., Study Design: This retrospective cohort study used hospital discharge records from the Premier Perspective database (Premier Inc., Charlotte, NC) of infants ≤ 36 weeks' gestational age who were discharged home after birth hospitalization during the November-March respiratory syncytial virus (RSV) seasons from 2006 to 2011. Descriptive statistics were performed and logistic regression was employed to identify differences in categorical variables., Results: Among infants ≤ 36 weeks' gestational age discharged home during the RSV seasons, 21.4 to 27.0% had a record of palivizumab receipt before discharge. Among infants ≤ 30 weeks' gestational age, palivizumab receipt was 82.3 to 88.8%. Receipt varied considerably at the hospital level, from 0 to 100%., Conclusion: This study improves our understanding of characteristics associated with predischarge palivizumab administration. The identified gaps in recommended care can help inform future implementation of palivizumab and other interventions to help improve the health of high-risk preterm infants in the United States., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aim: Palivizumab is reported to be effective in reducing respiratory syncytial virus hospitalisation. Its licensed uses include infants younger than six months of age, born before 35 weeks of gestation or under two years old with congenital heart disease or bronchopulmonary dysplasia. We redressed lack of research in the Netherlands by studying whether infants who met the licensed indications received the drug., Methods: Data were obtained from the PHARMO Database Network and The Netherlands Perinatal Registry for all linked infants born between 1 April 1999 and 31 March 2007. Determinants for receiving palivizumab were examined using logistic regression analyses., Results: Only 15% of the 3321 infants who met the licensed indications received palivizumab and the strongest predictor was being born before 32 weeks of gestation, with an odds ratio of 49.1 (95% confidence interval 31.5-76.4). However, 50% of infants born before 32 weeks did not receive palivizumab and the subanalyses showed that the probability increased for infants born in later years, those who had respiratory distress syndrome and those hospitalised during the respiratory syncytial virus season., Conclusion: Only 15% of eligible infants in the Netherlands received palivizumab and they were mostly born before 32 weeks, in line with Dutch guidelines., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: 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., Methods: 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., Results: 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., Conclusion: 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., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)