Syncytial Virus Infection In Infants Research Articles

Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of <24 months during anti-tumor therapy from April 2006 to March 2009 were investigated by sending a questionnaire to all member institutions of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

Risk of respiratory syncytial virus infection in infants with congenital cystic lung disease.

Congenital cystic lung disease (CCLD), which includes congenital cystic adenomatoid malformation, bronchopulmonary sequestration, and congenital lobar emphysema, has been reported to increase the risk of recurrent respiratory infection. In particular, respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in high-risk infants. The objective of this study was to investigate the risk of severe RSV infection in infants with CCLD. Infants antenatally diagnosed as having CCLD and admitted to a neonatal intensive care unit at the National Center for Child Health and Development in Tokyo between September 2002 and October 2011 were included in this study. We investigated retrospectively whether the infants were hospitalized with RSV infection by 24 months of age using their medical records. Forty-eight infants were antenatally diagnosed as having CCLD. Of the 48 infants, four (8.3%) were hospitalized with RSV infection by 24 months of age. Infants with CCLD have increased risk of severe RSV infection.

Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants.

Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. IL-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared to adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, while exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I (RIG-I) agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A+ γδ T cells compared to PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates.

Respiratory syncytial virus infections in infants affected by primary immunodeficiency.

Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population.

The Source of Respiratory Syncytial Virus Infection In Infants: A Household Cohort Study In Rural Kenya

Background. Respiratory syncytial virus (RSV) vaccine development for direct protection of young infants faces substantial obstacles. Assessing the potential of indirect protection using different strategies, such as targeting older children or mothers, requires knowledge of the source of infection to the infants.Methods. We undertook a prospective study in rural Kenya. Households with a child born after the preceding RSV epidemic and ≥1 elder sibling were recruited. Nasopharyngeal swab samples were collected every 3–4 days irrespective of symptoms from all household members throughout the RSV season of 2009–2010 and tested for RSV using molecular techniques.Results. From 451 participants in 44 households a total of 15 396 nasopharyngeal swab samples were samples were collected, representing 86% of planned sampling. RSV was detected in 37 households (84%) and 173 participants (38%) and 28 study infants (64%). The infants acquired infection from within (15 infants; 54%) or outside (9 infants; 32%) the household; in 4 households the source of infant infection was inconclusive. Older children were index case patients for 11 (73%) of the within-household infant infections, and 10 of these 11 children were attending school.Conclusion. We demonstrate that school-going siblings frequently introduce RSV into households, leading to infection in infants.

Potential for Palivizumab Interference With Commercially Available Antibody–antigen Based Respiratory Syncytial Virus Diagnostic Assays

Palivizumab is a monoclonal antibody indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus infection in infants. The potential for palivizumab to interfere with commercially available respiratory syncytial virus diagnostic tests was demonstrated. Negative test results in palivizumab-treated subjects should be interpreted with caution and confirmed by a nucleic acid amplification-based assay.

Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy

BackgroundRespiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing.MethodsA retrospective cohort study examined children born at ≥32 weeks gestation between 1996–2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions.ResultsThe study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32–33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03–1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49–4.50).ConclusionsLaboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.

Respiratory syncytial virus infections in infants and children with congenital heart disease

Lower respiratory tract infections multiply morbidity and mortality within patients with significant congenital heart disease (CHD). For respiratory syncytial virus (RSV), one of the most important pathogens, immunoprophylaxis with palivizumab has successfully been introduced. The question is which patients will benefit most from this costly preventive treatment. The era after the introduction of palivizumab has revealed a steep decrease in mortality. The markers of success - hospital stays, admission to the intensive care unit, days on mechanical ventilation, and death - consistently favor immunoprophylaxis. The key point of treatment success remains in all cases a careful patient selection, adherence to a time limit of 30 days between the injections and early use after cardiac surgery with cardiopulmonary bypass, as well as avoidance of nosocomial-acquired infections. Preventive therapy with palivizumab in patients with CHD has been investigated in terms of operating efficiency - with the lowest costs per quality-adjusted life years compared with preterm infants with or without bronchopulmonary dysplasia. The burden of RSV disease will decline, once a vaccine is available. Meanwhile, immunoprophylaxis with palivizumab is a useful tool for high-risk patients to reduce comorbidity and fatal outcome. Pharmacoeconomic considerations measuring quality-adjusted life years indicate important information about cost-effectiveness.

Respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants

BackgroundRespiratory Syncytial Virus (RSV) is the most important cause of severe respiratory infections in infants with seasonal epidemics. Environmental factors (temperature, humidity, air pollution) could influence RSV epidemics through their effects on virus activity and diffusion.MethodsWe conducted a retrospective study on a paediatric population who referred to our Paediatric Emergency Unit in order to analyze the correlation between weekly incidence of RSV positive cases during winter season in Bologna and meteorological factors and air pollutants concentration.ResultsWe observed a significant correlation between the incidence of RSV infections and the mean minimum temperature registered during the same week and the previous weeks.The weekly number of RSV positive cases was also correlated to the mean PM10 concentration of the week before.ConclusionsRSV epidemic trend in Bologna (Italy) is related to the mean minimum temperature, and the mean PM10 concentration.

Elevated risk of asthma after hospitalization for respiratory syncytial virus infection in infancy

Severe respiratory syncytial virus (RSV) infection in infancy is associated with substantial morbidity worldwide; whether it is a risk factor for childhood asthma is contentious. A systematic review of 28 articles was conducted, summarizing estimates of asthma risk after RSV hospitalization during infancy. Prevalence estimates of asthma, among those hospitalized for RSV in infancy, were from 8% to 63%, 10% to 92%, and 37%, at ages <5, 5 to 11, and ≥ 12 years, respectively. These rates were higher than those among non-hospitalized comparisons. The attributable risk of asthma due to RSV ranged from 13% to 22% and from 11% to 27% among children aged ≤ 5 and aged 5 to 11, respectively, and was 32% among children ≥ 12 years of age. Overall, 59% of asthma prevalence estimates from those previously hospitalized for RSV exceeded 20%, compared to only 6% of non-hospitalized comparison estimates. Despite variability in asthma prevalence estimates after RSV-related hospitalization, available data suggest a link between severe RSV infection in infancy and childhood asthma.

Strategies for Reducing the Risk of Respiratory Syncytial Virus Infection in Infants and Young Children: A Canadian Nurses’ Perspective

Respiratory syncytial virus (RSV) infections are prevalent globally and can cause substantial morbidity in infants and young children. The virus is easily transmitted by direct hand-to-hand contact and can lead to serious respiratory disease and hospitalization, particularly in premature infants and children with certain medical conditions. Educating families with young children, especially those in remote rural regions, regarding the potential adverse health outcomes of RSV infection and measures to reduce the risk of transmitting or acquiring RSV has been a key focus of the health care system in Canada. Geographic, cultural, and socioeconomic factors present formidable challenges to the execution of this endeavor. Therefore, it is critical to develop and systematically implement effective educational programs for both families and health care providers. In Canada, nurses play a critical role in education and counseling. In this review, we share our perspectives and suggest empirical practices that may be applicable worldwide.

Mortality and morbidity among infants at high risk for severe respiratory syncytial virus infection receiving prophylaxis with palivizumab: A systematic literature review and meta-analysis

A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease). MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies. Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab. Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis. A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses. Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.

Changes in helper lymphocyte chemokine receptor expression and elevation of IP‐10 during acute respiratory syncytial virus infection in infants

It is known that lymphopenia caused by apoptosis may occur during severe respiratory syncytial virus (RSV) infection. However, further evidence about how T-cell subsets may be affected in infants during severe RSV bronchiolitis is needed to understand the mechanisms through which immunological memory may be altered. There is increasingly convincing evidence that RSV may be associated with the development of atopy and asthma. Surrogates of Th1, Th2 and regulatory T-lymphocyte populations were measured in blood from children with acute RSV bronchiolitis and in convalescence using the cell surface receptors CXCR3, CCR4 and CD25, respectively. Samples were also obtained from healthy age-matched controls. Plasma levels of the chemokines interferon-γ inducible protein-10 (IP-10) and thymus and activation-regulated chemokine (TARC), which are known ligands for CXCR3 and CCR4, were also measured. Free plasma DNA was measured using quantitative PCR. CXCR3-positive cells were significantly decreased during acute infection (p = 0.013), while CCR4 and CD25 T-cell populations were unchanged. Plasma levels of IP-10 were markedly elevated in acute infection (p = 0.001). Convalescent samples were not significantly different to control samples for lymphocyte phenotypes or plasma chemokines. Elevated free plasma DNA was detected during acute infection compared with convalescence and controls. A profound reduction in the Th1, but not Th2, and CD25-positive lymphocyte populations associated with exaggerated IP-10 production occurs in severe RSV bronchiolitis. Free DNA is detectable in plasma. This may allow significant alterations in the generation of T-cell memory.

A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants.

Severe primary respiratory syncytial virus (RSV) infections are characterized by bronchiolitis accompanied by wheezing. Controversy exists as to whether infants suffer from virus-induced lung pathology or from excessive immune responses. Furthermore, detailed knowledge about the development of primary T-cell responses to viral infections in infants is lacking. We studied the dynamics of innate neutrophil and adaptive T-cell responses in peripheral blood in relation to the viral load and parameters of disease in infants admitted to the intensive care unit with severe RSV infection. Analysis of primary T-cell responses showed substantial CD8(+) T-cell activation, which peaked during convalescence. A strong neutrophil response, characterized by mobilization of bone marrow-derived neutrophil precursors, preceded the peak in T-cell activation. The kinetics of this neutrophil response followed the peak of clinical symptoms and the viral load with a 2- to 3-day delay. From the sequence of events, we conclude that CD8(+) T-cell responses, initiated during primary RSV infections, are unlikely to contribute to disease when it is most severe. The mobilization of precursor neutrophils might reflect the strong neutrophil influx into the airways, which is a characteristic feature during RSV infections and might be an integral pathogenic process in the disease.

Motavizumab for the prevention of respiratory syncytial virus infection in infants

Background: Respiratory syncytial virus (RSV) is the most important respiratory viral pathogen of infancy. The only unequivocally effective pharmacological compound for the management of RSV infection is palivizumab, a monoclonal antibody against the fusion protein of RSV. Recently, motavizumab, a similar but more potent monoclonal antibody, has been developed and tested against palivizumab. Objective: In this review, we summarize data comparing the safety and efficacy of the two monoclonal antibodies in prevention of RSV infection. Other therapeutic options also are discussed. Methods: We reviewed all published articles listing motavizumab or palivizumab in the title or keywords. Results/conclusion: In a large comparative clinical trial for which peer review is pending, motavizumab proved noninferior to palivizumab for prevention of RSV-related hospital admission in infants with underlying conditions placing them at high risk for hospitalization after RSV infection. In this trial, motavizumab in comparison to palivizumab significantly reduced the severity of illness among those infants hospitalized with RSV infection, as well as the number of outpatient lower respiratory infections caused by RSV. Safety profiles of each of the two compounds were excellent. Based on these data, motavizumab should eventually replace palivizumab in the prevention of RSV infection.

Asthma and allergy development in mono-zygotic twins discordant for severe respiratory syncytial virus infection in infancy

Asthma and allergy development in mono-zygotic twins discordant for severe respiratory syncytial virus infection in infancy

Respiratory syncytial virus infection in infants admitted to paediatric intensive care units in London, and in their families

We carried out a study in five London paediatric intensive care units (PICUs), with the objectives of describing a cohort of infants with respiratory syncytial virus (RSV) infection, comparing hospital diagnosis with PCR results and investigating the spread of RSV in families. Eligible infants were under 5 months old and admitted betweem November 1998 and October 1999 with respiratory failure, apnoea and/or bradycardia or acute life threatening episodes (ALTE). We diagnosed RSV by PCR analysis of nasopharyngeal aspirate, and in contacts by PCR of pernasal swabs. Of the 137 eligible infants, 66% (91/137) were recruited; of these, 82% (75/91) had RSV, with 47% (35/75) diagnosed by hospital laboratory tests and 93% (70/75) by PCR. The median duration of ventilation was 4.4 days, the length of stay on PICU, 8.6 days, and the length of stay in hospital, 15.9 days. In most families (62%), the parents and siblings developed symptoms of RSV infection at the same time as the infant. When the index infant was a secondary case, primary cases occurred in both older siblings (16 families) and adults (11 families). Silent RSV infection occurred frequently amongst children and adults. RSV is under-diagnosed in PICUs. PCR increases the rate of diagnosis of RSV compared to routine hospital diagnostic methods. Young infants are most often infected at the same time as or before their parents and siblings, indicating that the source may be outside the household; vaccinating family members may not prevent RSV infection in infants.

Optimizing the delivery and use of a new monoclonal antibody in children with congenital heart disease: A successful provincial respiratory syncytial virus prophylaxis program

To describe a program for passive immunization against respiratory syncytial virus infection in infants with hemodynamically significant congenital heart disease (CHD) in accordance with the Canadian Paediatric Society recommendations. A provincial coordinating committee composed of specialists in pediatrics, cardiology, infectious diseases, neonatology and public health collaborated to develop and implement a program to identify children with hemodynamically significant heart disease and offer respiratory syncytial virus prophylaxis. Database records for all children younger than two years of age who were seen by the provincial pediatric cardiology referral service were reviewed. Children with hemodynamically significant heart disease, as determined by a clinical assessment and echocardiography, were considered to be eligible for monthly palivizumab prophylaxis for five winter months. All physicians in the province were notified that approval of the provincial cardiology service was required for prophylaxis to be administered. Immunization rates were compared with projected rates based on the expected population-based immunization rates in infants with CHD in other provinces. 401 children with any cardiac diagnoses were identified, representing 545 potential patient-seasons of prophylaxis over two years in a birth cohort of 20,173 and 19,227 children, in each respective season (13.8 patient-seasons per 1000 births). Of these, 21 children were eligible for palivizumab prophylaxis according to the Canadian Paediatric Society criteria. All eligible children were immunized, and no ineligible children received the immunization. A review of palivizumab use in other provinces revealed highly variable rates of prophylaxis. The use of palivizumab for children with CHD can be optimized through a provincial model, in which children requiring prophylaxis are prospectively identified and reviewed by pediatric cardiologists -- and to whom evidence-based guidelines developed by a multidisciplinary team -- are applied. Such a model ensures that all patients requiring prophylaxis receive the appropriate immunization and avoids the immunization of low-risk children with CHD, in whom the benefits of palivizumab have not been proven.

How Viral Infections Cause Exacerbation of Airway Diseases

Exacerbations of asthma and COPD are major causes of morbidity, mortality, and health-care costs. Over the last decade, studies using new molecular diagnostic techniques have established that respiratory viruses are a major cause of exacerbations of both asthma and COPD. The most prevalent viruses detected during exacerbations are the rhinoviruses. Despite the burden of disease associated with exacerbations, little is known about the mechanisms of virus-induced exacerbations of airway diseases. Exacerbations are associated with increased airway inflammation in patients with both asthma and COPD, but many questions remain unanswered regarding the key inflammatory cells and mediators involved. Identifying the key inflammatory mediators involved in exacerbations holds the promise of developing diagnostic and prognostic markers of exacerbation. In addition, such studies can identify new therapeutic targets for the development of novel drugs for the prevention and treatment of exacerbations.

Prevention and treatment of respiratory syncytial virus infection in infants: an update

Respiratory syncytial virus (RSV) is a serious pathogen causing significant mortality and morbidity, especially in premature infants and infants with chronic lung disease or significant congenital heart disease. Therapy for RSV infection is essentially supportive, although several new compounds are under investigation. Therefore, immunoprophylaxis to prevent severe RSV disease in high-risk infants assumes great significance. Palivizumab, a humanized monoclonal antibody to RSV, significantly reduces hospitalization in the first 6 months in premature infants born at less than 35 weeks, infants less than 24 months of age with chronic lung disease and requiring treatment in the last 6 months, and in children 24 months or younger with hemodynamically significant heart disease. A new ultrapotent anti-RSV antibody (MEDI-524™) appears to be more effective in animals than palivizumab and is undergoing clinical evaluation. There has been considerable progress in the development of vaccines; namely subunit, live attenuated, genetically recombinant virus and polypeptide vaccines. Plasmid DNA vaccines coding for parts of the F and G surface glycoproteins and vaccinia vector vaccines are also being evaluated. Maternal immunization has the potential to prevent RSV disease in early infancy. RSV prophylaxis has seen tremendous progress in the last decade.