Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.
The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for \"respiratory syncytial virus\", \"RSV\", \"lower respiratory tract infection\", \"bronchiolitis\", \"acute\", \"viral pneumonia\", \"neonatal\", \"infant\" \"children\", and \"pediatric\".
Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out.
This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Uniformity and compliance with clinical practice guidelines (CPGs) for use of palivizumab in preventing severe respiratory syncytial viral infection in Australian high-risk infants remain unclear.
An online survey was conducted across the Australian and New Zealand Neonatal Network (ANZNN) to determine clinical practices around palivizumab. A literature search was also performed to identify and compare national and international guidelines.
A total of 65 of 422 ANZNN members completed the survey. Respondents included 61 senior medical staff of consultants/staff specialists (78%) and four nursing staff (6%). According to the survey, infants most likely to be recommended palivizumab included preterm infants born <29 weeks gestational age (GA) (30%), children with chronic lung diseases (CLDs) born <32 weeks GA (40%), and with hemodynamically significant heart disease (35%). Many of the respondents (53%) stated that CPGs for palivizumab were developed locally. Literature search identified 20 guidelines (10 international and 10 domestic); 16 (80%) recommended palivizumab use in preterm infants, 16 (80%) recommended use in infants with CLD, 17 (85%) in congenital heart disease and 6 (30%) in bronchopulmonary dysplasia (BPD). Eight (40%) guidelines provided specific recommendations for immunocompromised infants. Canada, Western Australia, and American Academy of Paediatrics provided recommendations for Indigenous children. Frequency and dosage of palivizumab was universal across all CPGs. None of the international guidelines obtained were from low- or middle-income countries.
Standardization of CPGs may improve clinical decision making around use of palivizumab in high-risk infants.

Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe.
We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting.
A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency.
We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.

Respiratory syncytial virus (RSV) is the major viral cause of infant and childhood lower respiratory tract disease worldwide. Defining the optimal target product profile (TPP) is complicated due to a wide range of possible vaccine properties, modalities and an incomplete understanding of the mechanism of natural immunity. We report consensus population level impact projections based on two mathematical models applied to a low income setting.
Two structurally distinct age-specific deterministic compartmental models reflecting uncertainty associated with the natural history of infection and the mechanism by which immunity is acquired and lost were constructed. A wide range of vaccine TPPs were explored including dosing regime and uptake, and effects in the vaccinated individual on infectiousness, susceptibility, duration of protection, disease severity and interaction with maternal antibodies and natural induced immunity. These were combined with a range of vaccine implementation strategies, targeting the highest priority age group and calibrated using hospitalization data from Kilifi County Hospital, Kenya.
Both models were able to reproduce the data. The impact predicted by the two models was qualitatively similar across the range of TPPs, although one model consistently predicted higher impact than the other. For a proposed realistic range of scenarios of TPP combinations, the models predicted up to 70% reduction in hospitalizations in children under five years old. Vaccine designs which reduced the duration and infectiousness of infection were predicted to have higher impacts. The models were sensitive to the coverage and rate of loss of vaccine protection but not to the interaction between vaccine and maternal/naturally acquired immunity.
The results suggest that vaccine properties leading to reduced virus circulation by lessening the duration and infectiousness of infection upon challenge are of major importance in population RSV disease control. These features should be a focus for vaccine development.

The American Academy of Pediatrics (AAP) recently narrowed the indications for respiratory syncytial virus (RSV) prophylaxis, while in Israel the guidelines have not changed.
To compare the prevalence and severity of RSV infection among preterm infants born earlier than 340/7 weeks of gestation (PI), late preterm infants born at 340/7-366/7 weeks (LPTI), and term infants born after 370/7 weeks of gestation (TI) and to determine whether the results support a change in local policy.
Data of all children aged 0-14 years hospitalized with PCR-positive RSV in a single tertiary center from 2010 to 2014 were collected. A total of 793 children were included and divided into 3 groups: 637 were TI, 105 were LPTI, and 50 were PI. These groups were compared regarding incidence of hospitalization due to RSV infection, intensive care unit (ICU) hospitalization, and length of hospitalization.
The hospitalization rate due to RSV infection was 5.2, 3.5, and 1.3% among PI, LPTI, and TI, respectively (p < 0.01). The hospitalization rate in the ICU was 24, 7.6, and 3% among PI, LPTI, and TI, respectively (p < 0.001). The length (days) of hospitalization was significantly longer among PI compared with LPTI and TI (p < 0.001). Overall, the hospitalization rate and disease severity were significantly higher for infants born earlier than 35 weeks of gestation compared with more maturely born infants.
RSV infection remains a major cause of morbidity among children born prematurely even after RSV prophylaxis and would probably be greater were prophylaxis curtailed. Our results do not support applying the current AAP guidelines in Israel. Further local studies are needed to optimize prophylaxis for both PI and LPTI.

Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system. Owing to differences in screening, clinical presentation, and therapy for influenza and adenovirus, ECIL-4 recommendations are summarized for CARVs other than influenza and adenovirus.

OBJECTIVE: To determine the effect of an interventional program designed to improve adherence to American Academy of Pediatrics (AAP) guidelines for palivizumab prophylaxis.
METHODS: The study was carried out at the Children\'s Hospital, University of California, Irvine Medical Center and its affiliated clinics. An interventional program focusing on education of health care workers on AAP guidelines, updating health care providers about respiratory syncytial virus (RSV) activity, as well as designating a single clinic with effective screening of referrals for administration of palivizumab, was implemented during the summer of 2004. The medical records of infants who had received at least 1 dose of palivizumab or were eligible to receive palivizumab during the 2003-2004 and the 2004-2005 RSV seasons at the University of California, Irvine Medical Center were reviewed. The proportion of patients who received injections according to AAP guidelines was compared.
RESULTS: After the intervention, the proportion of patients who received palivizumab injections according to AAP recommendations increased from 39% to 61% (P < 0.0001). The program decreased the proportion of unnecessary injections significantly (140/525, or 27%, in 2003-2004 to 33/323, or 10%, in 2004-2005; P < 0.0001) but did not change the proportion of missing injections. The program resulted in a significant drop (14% to 2%; P < 0.0001) in proportion of palivizumab injections that were given too late, when RSV activity had subsided. RSV hospitalization rates did not change as a result of the intervention.
CONCLUSIONS: Our interventional program improved adherence to AAP guidelines mainly by decreasing the unnecessary palivizumab injections.

The F (fusion) protein of the respiratory syncytial viruses is synthesized as an inactive precursor F(0) that is proteolytically processed at the multibasic sequence KKRKRR(136) into the subunits F(1) and F(2) by the cellular protease furin. This maturation process is essential for the F protein to gain fusion competence. We observed that proteolytic cleavage additionally occurs at another basic motif, RARR(109), that also meets the requirements for furin recognition. Cleavage at both sites leads to the removal from the polypeptide chain of a glycosylated peptide of 27 amino acids. When the sequence RARR(109) was changed to NANR(109) or to RANN(109) by site-directed mutagenesis, cleavage by furin was completely prevented. Although the mutants were still processed at position Arg(136), they did not show any syncytia formation. Proteolytic cleavage of the modified motifs was achieved by treatment of transfected cells with trypsin converting the F mutants into their fusogenic forms. Our findings indicate that both furin consensus sequences have to be cleaved in order to activate the fusion protein.

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