Respiratory syncytial virus disease in preterm infants in the U.S. born at 32-35 weeks gestation not receiving immunoprophylaxis.

BACKGROUND: The Respiratory Syncytial Virus (RSV) Respiratory Events Among Preterm Infants Outcomes and Risk Tracking (REPORT) study evaluated RSV disease burden in U.S. preterm infants 32-35 weeks gestational age (wGA) not receiving RSV prophylaxis. METHODS: Preterm infants <6 months of age as of November 1st were followed prospectively at 188 clinics from September to May 2009-2010 or 2010-2011. Nasal and pharyngeal swabs were collected for medically attended acute respiratory illnesses (MAARI) and tested for RSV by qRT-polymerase chain reaction. Risk factors were assessed using multivariate Cox proportional hazard model adjusted for seasonality. RESULTS: Of 1642 evaluable infants, 287 experienced RSV MAARI. Rates of RSV-related MAARI, outpatient lower respiratory tract illness, emergency department visits and hospitalization (RSVH) during November to March were 25.4, 13.7, 5.9 and 4.9 per 100 infant-seasons, respectively. Preschool-aged, nonmultiple-birth siblings and daycare attendance were consistently associated with increased risk of RSV. RSVH rates were highest in infants 32-34 and 35 wGA who were <6 months of age during November to March with daycare attendance or nonmultiple-birth, preschool-aged siblings (8.9 and 9.3 per 100 infant-seasons, respectively, versus 3.5 for all other infants, P<0.001). Chronologic age <3 months was associated with a higher RSVH rate for infants 35 wGA but not for infants 32-34 wGA. CONCLUSIONS: In US preterm infants who were 32-35 wGA, <6 months on November 1st and not receiving RSV prophylaxis, the burden of RSV MAARI was 25 per 100 infant-seasons. The highest RSVH rates occurred among those with daycare attendance or nonmultiple-birth, preschool-aged siblings while they were <6 months of age during the RSV season.

Definition and outpatient management of the very low-birth-weight infant with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of prematurity, is the major cause of pulmonary disease in infants. The pathophysiology and management of BPD have evolved over the past four decades as improved neonatal intensive care unit (NICU) modalities have increased survival rates. The likelihood for developing BPD increases with the degree of prematurity and reaches 25-35% in very low-birth-weight and extremely low-birth-weight infants. BPD affects many organ systems, and infants with BPD are at increased risk for rehospitalization and numerous complications following NICU discharge. The management of BPD and medically related problems, particularly during the first 2 years of life, remains a continuing challenge for parents and healthcare providers. It is important that a multidisciplinary team consisting of the neonatologist/attending physician, primary care physician, and other specialized support staff work in concert and meet regularly to provide continuity of care and accurate patient assessments.

Respiratory syncytial virus hospitalization trends in infants with chronic lung disease of infancy, 1998-2008.

OBJECTIVE: Infants with chronic lung disease of infancy (CLDI) are at high risk for severe respiratory syncytial virus (RSV) illness requiring hospitalization. Palivizumab was first licensed in 1998 for the prevention of RSV disease in high-risk infants, including those with CLDI. We performed a retrospective cohort study of all hospitalized children with CLDI aged <2 years between 1998 and 2008 in the USA to determine trends in rates of hospitalizations due to RSV (RSVH) since the launch of palivizumab. MATERIALS AND METHODS: Data from the United States National Hospital Discharge Survey, a multistage systematic survey sample of US hospitals, were assembled. We defined RSVH using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Quarterly rates of RSVH were assessed for children with CLDI (ICD-9-CM code 770.7) and calculated between 1998 and 2008. Because RSV may be miscoded, the analysis was repeated after expanding the definition of RSVH to include all acute bronchitis and acute bronchiolitis (ABH) (ICD-9-CM = 466). Trends were described using linear regression with seasonal indicators included in the model. RESULTS: On average, about 966 RSVH (range 98-1373 RSVH) per year were found for children <2 years with CLDI in the USA between 1998 and 2008. Over the 11-year period, the predicted rate of RSVH statistically significantly decreased by 48% (from 93.78 to 49.06 RSVH per 1 million children) (P = 0.013). Addition of ABH resulted in a nonstatisically significant decrease of 32% over the 10-year period (P = 0.102). CONCLUSION: These results suggest that there has been a decrease in the rate of RSVH in infants with CLDI between 1998 and 2008. The reasons for this decrease may include improved neonatal intensive care unit and outpatient management of CLDI, and possibly increased use of palivizumab in this high-risk population.

Prevention of serious respiratory syncytial virus-related illness. II: Immunoprophylaxis.

Respiratory syncytial virus (RSV) causes significant morbidity in very young children, preterm infants with and without chronic lung disease, and children with hemodynamically significant congenital heart disease. In the absence of a safe and effective vaccine, alternative means of protecting high-risk infants and young children from serious RSV illness have been studied. Clinical observations and animal model data over the past 30 years suggested that RSV immunoglobulin G (IgG) neutralizing antibodies might offer protection from severe RSV lower respiratory tract disease. Transfer of adequate amounts of IgG to the fetus does not occur efficiently until the third trimester of pregnancy, which helps to explain why premature infants are at high risk of serious RSV illness. Efforts shifted toward the prophylactic monthly administration of standard immunoglobulins and, later, of RSV-enriched immunoglobulin in selected high-risk infants and young children. Although this approach proved effective, RSV-enriched immune globulin was not suitable for all patients and administration was labor intensive. The development of palivizumab, a monoclonal antibody that can bind to a specific antigenic site on the virus and prevent cell-to-cell spread of infection has since become the mainstay of RSV illness prevention in preterm infants and those with significant congenital heart disease. Palivizumab, the only monoclonal antibody approved for the prevention of RSV lower respiratory tract disease must be administered monthly throughout the RSV season and does not always prevent serious RSV illness. Further research to develop more effective and less labor-intensive immunoprophylactic agents is ongoing.

Prevention of serious respiratory syncytial virus-related illness. I: Disease pathogenesis and early attempts at prevention.

Respiratory syncytial virus (RSV) was first described 160 years ago but was not officially recognized as a cause of serious illness in children until the late 1950s. It has been estimated that virtually all children have had at least one RSV infection by their second birthday. RSV is responsible for annual disease outbreaks, usually during a defined winter seasonal period that can vary by community and year. RSV is recognized as the leading cause of hospitalization among young children worldwide. Infants of young chronologic age and children with predisposing factors, such as premature birth, pulmonary disease, or congenital heart disease, are most susceptible to serious illness. Unlike other viruses, immunity to RSV infection is incomplete and short lived, and reinfection is common throughout life. Initial attempts to develop a vaccine in the 1960s met with unexpected and tragic results; many children vaccinated with a formalin-inactivated wild-type virus developed serious pulmonary disease upon subsequent natural infection. Numerous other vaccine technologies have since been studied, including vectored approaches, virus-like particles, DNA vaccines, and live attenuated virus vaccine. As of early 2010, only two companies or institutions had RSV vaccine candidates in early clinical trials, and no vaccine is likely to be licensed for marketing in the immediate future.

Trends in chronologic age and infant respiratory syncytial virus hospitalization: an 8-year cohort study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children and the leading cause of hospitalization in infants aged <1 year. METHODS: We examined trends in RSV hospitalization (RSVH) among infants from 1998 to 2006, using the United States (US) National Hospital Discharge Survey (NHDS) database. RSVH was defined by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Age at the time of hospitalization was determined using NHDS birth records; RSVH rates were analyzed for infants grouped into three age cohorts (<3 months, 3 to 6 months, and >6 to <24 months). Trends in hospitalization rates were evaluated using linear regression. Relative rates (RR) and 95% confidence intervals (CI) were computed to compare average RSVH rates for infants across age-specific groups. The annual proportion of RSVH by age group was also calculated. RESULTS: Approximately 1.1 million (90,000-147,000 per year) RSVHs in predominantly term children aged <24 months were analyzed. Compared with children aged >6 to <24 months, rates for RSVH were significantly higher among infants aged <3 months (RR, 7.38; 95% CI, 7.35-7.41) and infants aged 3 to 6 months (RR, 5.28; 95% CI, 5.26-5.29). The proportion of RSVH in the first year of life was lowest among infants aged <1 month (9%). [corrected] The greatest proportion of RSVH was observed in children aged 3 to 6 months (14%-23% RSVH per year; chi-square P<0.0001). When the definition of RSVH was expanded to include unspecified hospitalizations for acute bronchiolitis, similar results were observed. CONCLUSION: RRs were highest among the <3- month and 3- to 6-month age groups. The highest proportion of RSVH was among the 3- to 6-month age group. Analysis of the impact of RSV season, clinical practices, and other factors on these trends is warranted.

Preliminary clinical findings on NEUMUNE as a potential treatment for acute radiation syndrome.

5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and treat infection and radiation-induced immune suppression. We here report on the safety, tolerability and haematologic activity of 5-AED in four double-blinded, randomized, placebo-controlled studies on healthy adults including elderly subjects. A 5-AED injectable suspension formulation (NEUMUNE) or placebo was administered intramuscularly as either a single injection, or once daily for five consecutive days at doses of 50, 100, 200 or 400 mg. Subjects (n = 129) were randomized to receive NEUMUNE (n = 95) or the placebo (n = 34). NEUMUNE was generally well-tolerated; the most frequent adverse events were local injection site reactions (n = 104, 81%) that were transient, dose-volume dependent, mild to moderate in severity, and that resolved over the course of the study. Blood chemistries revealed a transient increase (up to 28%) in creatine phosphokinase and C-reactive protein levels consistent with intramuscular injection and injection site irritation. The blood concentration profile of 5-AED is consistent with a depot formulation that increases in disproportionate increments following each dose. NEUMUNE significantly increased circulating neutrophils (p < 0.001) and platelets (p < 0.001) in the peripheral blood of adult and elderly subjects. A dose-response relationship was identified. Findings suggest that parenteral administration of 5-AED in aqueous suspension may be a safe and effective means to stimulate innate immunity and alleviate neutropenia and thrombocytopenia associated with ARS.

The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children.

BACKGROUND: Although respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) in early life are followed by later airway hyperreactivity, it is unclear whether there is a causal relationship between this and an atopic diathesis. OBJECTIVES: To separate the effects of RSV LRTI and an atopic diathesis on subsequent recurrent wheezing, we examined the protective effect of previous palivizumab administration against subsequent recurrent wheeze in infants with and without a family history of atopy. METHODS: A prospective multicenter, matched, double cohort study was conducted in 27 centers in Europe and Canada. The rates of physician-diagnosed recurrent wheezing in premature infants <36 weeks gestation who had received palivizumab in the first year of life were compared to those of gestational age-matched controls. RESULTS: The relative protective effect of palivizumab on physician-diagnosed recurrent wheezing through the ages of 2 to 5 years was 68% in those with no family history of asthma (odds ratio, 0.32; (95% CI, 0.14-0.75; N = 146 palivizumab-treated, 171 untreated) and 80% in those with no family history of atopy or food allergies (odds ratio, 0.20; 95% CI, 0.07-0.59; N = 101 palivizumab-treated, 100 untreated). In contrast, there was no effect of palivizumab on subsequent recurrent wheezing in the 90 children with a family history of atopy or food allergies compared to 130 untreated infants with atopic families. CONCLUSION: Respiratory syncytial virus prophylaxis in nonatopic children decreases by 80% the relative risk of recurrent wheezing but does not have any effect in infants with an atopic family history. This suggests that RSV predisposes to recurrent wheezing in an atopy-independent mechanism.

A novel active respiratory syncytial virus surveillance system in the United States: variability in the local and regional incidence of infection.

BACKGROUND: To characterize the onset, peak, and duration of the RSV season in major metropolitan areas in the United States as determined from laboratory test data collected by a novel RSV surveillance program (RSV Alert), including regional and national trends. METHODS: We prospectively analyzed results of more than 600,000 tests collected weekly during 3 seasons (2004/2005-2006/2007) by the RSV Alert program. More than 200 institutions participated in the first 2 seasons of the program, and more than 600 sites in the third. Data were analyzed for trends in season onset, offset, and duration at the local, regional, and national levels. RESULTS: Considerable variability in season onset and duration was noted between metropolitan areas located geographically within the same region. Seasonal outbreaks of RSV consistently peaked first, concluded earliest, and were of longest duration in the Southern region. The onset of the RSV season occurred latest and peaked last in the Midwest region each season. CONCLUSIONS: The variable nature of outbreaks observed between metropolitan areas located geographically within the same regions of the country is highlighted through data collected for 3 consecutive seasons. The RSV Alert program is a valuable reporting system that provides real-time surveillance data at a city/local level nationwide and has potential to aid clinicians in decisions regarding RSV management.

Use of Palivizumab for prevention of hospitalization as a result of respiratory syncytial virus in infants with cystic fibrosis.

The Palivizumab Outcomes Registry collected data on 19,548 high-risk infants who received > or =1 dose of palivizumab and followed prospectively from 2000 through 2004. Ninety-one children with cystic fibrosis (CF) were identified who received palivizumab off label. None of the infants with CF who received prophylaxis was hospitalized as a result of respiratory syncytial virus lower respiratory tract infection. Evaluations of palivizumab use in infants with CF could be warranted.

Respiratory syncytial virus infection in 406 hospitalized premature infants: results from a prospective German multicentre database.

Premature birth, chronic lung disease of prematurity (CLD), congenital heart disease and immunodeficiency predispose to a higher morbidity and mortality in respiratory syncytial virus (RSV) infection. This study describes the preterms hospitalised with RSV infection from the prospective German DSM RSV Paed database. The DMS RSV Paed database was designed for the prospective multicentre documentation and analysis of clinically relevant aspects of the management of inpatients with RSV infection. This study covers six consecutive RSV seasons (1999-2005); the surveillance took place in 14 paediatric hospitals in Germany. Of the 1,568 prospectively documented RSV infections, 26% (n=406) were observed in preterms [vs. 1,162 children born at term (74%)] and 3% (n=50) had CLD, of which 49 had received treatment in the last 6 months ('CLDplus'). A significantly higher proportion in the preterm group had congenital heart disease, nosocomial infection, and neuromuscular impairment. There were significantly more children older than 24 months in the preterm group. The attributable mortality was 0.2% (n=2) in children born at term vs. 1.2% (n=5) in the preterm group (p=0.015) [preterm plus CLD 8.0% (n=4 of 50); McIntosh grade 1, 8.6% (n=3 of 35) and McIntosh Grade 4, 15% (n=3 of 20)]. Eight patients were categorized as 'palivizumab failures'. In the multivariate analysis, premature birth, CLD(plus), and nosocomial infection were significantly and independently associated with the combined outcome 'complicated course of disease'. In conclusion, this is the first prospective multicentre study from Germany that confirms the increased risk for severe RSV disease in preterms, in particular in those with CLD treated in the last 6 months before the onset of the infection. From the perspective of our results, the statements of the German Society of Paediatric Infectious Diseases considering the use of passive immunisation (2003) seem reasonable.

Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing.

OBJECTIVE: Children who experience respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) early in life have high rates of subsequent recurrent wheezing. Palivizumab, an anti-RSV monoclonal antibody, has 78% to 80% efficacy in preventing RSV hospitalization in premature infants without chronic lung disease. We hypothesized that palivizumab, by ameliorating or preventing early RSV LRTI in preterm infants, might decrease later recurrent wheezing. STUDY DESIGN: A cohort of preterm infants who had received palivizumab and were not hospitalized for RSV (n = 191) or who never received palivizumab (n = 230; 76 who were hospitalized for RSV and 154 who were not), were prospectively followed for 24 months beginning at a mean age of 19 months. The subjects were assessed for recurrent wheezing by caretaker or physician report. RESULTS: The incidences of recurrent wheezing and physician-diagnosed recurrent wheezing were significantly lower in the 191 palivizumab-treated subjects (13% and 8%, respectively) compared with all 230 untreated subjects (26%, P = .001 and 16%, P = .011, respectively) and with the 154 patients in the subgroup not hospitalized for RSV LRTI (23%, P = .022 and 16%, P = .027, respectively). The effect of palivizumab treatment remained significant after adjustment for potential confounding variables. CONCLUSIONS: Our study suggests that preventing RSV LRTI with palivizumab may reduce subsequent recurrent wheezing in premature infants.

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. METHODS: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. RESULTS: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Nosocomial respiratory syncytial virus infection: impact of prospective surveillance and targeted infection control.

BACKGROUND: Nosocomially acquired respiratory syncytial virus (RSV) infections cause serious problems in hospitalized patients. An increased effort should be made to describe the problems connected with such infections in pediatric hospitals, with the aim of reducing the occurrence of nosocomial RSV infections (NI). METHODS: A specialized database was introduced for surveillance and a multifaceted barrier concept based on the CDC recommendations was developed for the control of NI in a university children's hospital in Germany. RESULTS: Between 1999 and 2002 (November 1-April 30), 283 RSV infections (general population) were prospectively documented. Thirty-nine cases (13.8%) were nosocomial infections (NI) with an incidence density (ID) of 0.99/1000 patient days; 48.7% of all NI were found in prematurely born infants. Following the introduction of a surveillance and prevention policy, a 9-fold decrease of the ID (1.67 vs. 0.18/1000 patient-days) was found when comparing the first and the last season. Intensive care treatment was required in 18% of all documented RSV-infections, in 48.7% of all NI cases and in 43.5% of all RSV-infected prematurely born infants. Overall RSV-related mortality was 0.71%. CONCLUSIONS: Early diagnosis, a strict cohorting and contact isolation policy, and prospective surveillance contribute to the reduction of nosocomial RSV infection.

Acute and long-term effects of infection by the respiratory syncytial virus in children with congenital cardiac malformations.

All newborn infants have limited pulmonary reserve compared with older children. This puts them at increased risk of respiratory complications, such as those associated with infection by the respiratory syncytial virus. Young children with congenital cardiac disease are particularly likely to suffer severe disease related to infection by the virus. In these children, the extreme vulnerability of the lung to pulmonary oedema is compounded by the additional burden caused by the respiratory syncytial virus. In addition to the well-documented acute pulmonary effects of infection with the respiratory syncytial virus, there may also be consequent long-term respiratory morbidity. Clinical studies have shown that infection by the virus in infancy is associated with a higher risk of developing subsequent bronchial obstructive disease. Much debate surrounds the mechanisms underlying this association. It is thought that a combined immunological and neurogenic response mechanism is likely. Prevention of severe respiratory disease in infants and young children with congenital heart disease due to infection by the virus may, therefore, offer both immediate and long-term benefits. Indeed, an increasing body of evidence supports this hypothesis, indicating a clinical rationale for prophylaxis against the virus in infancy, in order to reduce the chance of developing reactive airways disease and asthma in later life.

Respiratory syncytial virus and other pneumoviruses: a review of the international symposium--RSV 2003.

The Respiratory Syncytial Virus 2003 symposium took place from 8th-11th November 2003 in Stone Mountain, Georgia, and brought together more than 200 international investigators engaged in RSV research. RSV biology, pathogenesis, and clinical data, as well as RSV vaccines and antivirals, were addressed in the meeting, and this review will aim to briefly summarize and discuss the implications of new findings. The meeting also served as the inauguration of the Robert M. Chanock Award for lifetime achievement in RSV research, an award named in honor of the person who started the field of RSV research by recovering the first human RS virus from infants with severe bronchiolitis in 1956.

Randomized, open-label preference study of two cyclosporine capsule formulations (usp modified) in stable solid-organ transplant recipients.

BACKGROUND: Prior research has indicated patient dissatisfaction with the odor, size, and taste of cyclosporine capsules, as well as the halitosis and body odor the capsules can cause. OBJECTIVES: The purposes of this investigation were to (1) compare the overall cyclosporine capsule preference (Gengraf vs Neoral) in stable, solid-organ transplant recipients, (2) assess patient preference based on specific capsule attributes, and (3) determine the reliability of the Cyclosporine Capsule SatiSfaCtion Survey (original to this study). METHODS: In this multicenter, randomized, open-label, parallel-group, preference study, patients were recruited from 144 centers in North America with established transplant programs. Solid-organ transplant recipients who had taken stable doses of cyclosporine (Neoral) for >/=2 consecutive months were randomized in a 9:1 ratio to receive another cyclosporine formulation (Gengraf) or to remain on Neoral therapy. Patients completed the Cyclosporine Capsule Satisfaction Survey prior to randomization (baseline survey) and after taking the study drug for 4 weeks (final survey). The survey consisted of multiple attribute items with high face validity in assessing patients' perceptions and preferences with regard to their overall experience, as well as specific attributes of cyclosporine capsules known to affect patient acceptance. RESULTS: The intent-to-treat population included 1906 patients (1211 men, 693 women [sex unknown in 2 patients]; mean [SD] age, 50.2 [12.4] years). A total of 1708 patients were switched to Gengraf; 198 continued on Neoral. Based on their overall experience with both capsule formulations, the majority of patients switched to Gengraf (61.9%) responded that they preferred the Gengraf capsule, compared with 13.7% who preferred the Neoral capsule and 24.4% who indicated no preference (P < 0.001). A similar preference for Gengraf was observed based on capsule odor (66.3%), ease of swallowing (51.5%), taste (57.1%), and impact on breath odor (52.5%) and body odor (48.4%) (P < 0.001 for each test). The results of internal consistency and reproducibility calculations were high for the Cyclosporine Capsule Satisfaction Survey. Internal consistency ranged from alpha = 0.84 to 0.95 for the subscales and was alpha = 0.95 for the overall score. Ranges for reproducibility in the subscales were r = 0.75 to 0.79, with an overall reproducibility of r = 0.85. Guyatt's responsiveness statistics for the subscale and overall scores were moderately high to very high, indicating that the survey is capable of measuring change in response to treatment. CONCLUSIONS: Of the transplant recipients receiving Gengraf in this study, most preferred Gengraf to Neoral based on overall experience, capsule odor, difficulty swallowing, taste, breath odor, and body odor. Among all study patients, fewer patients receiving Gengraf were bothered by capsule odor, difficulty in swallowing, taste, or the impact on breath or body odor compared with patients who continued to receive Neoral. Internal consistency, reproducibility, and responsiveness results show that the Cyclosporine Capsule Satisfaction Survey is a psychometrically valid instrument that is appropriate for use in clinical trials.

Evaluation of the safety of palivizumab in the second season of exposure in young children at risk for severe respiratory syncytial virus infection.

BACKGROUND: Palivizumab reduces respiratory syncytial virus (RSV) hospitalisations in high-risk infants. Those with severe bronchopulmonary dysplasia may require two seasons of prophylaxis. There is concern that this humanised antibody might cause an adverse immune response in a second season of use. OBJECTIVE: To evaluate and compare the occurrence of anti-palivizumab antibodies and clinical adverse events in subjects receiving monthly palivizumab injections for a first and second season, and to assess frequency and severity of RSV disease in the two groups. DESIGN AND PATIENTS: Subjects aged or=1 : 80). Serum palivizumab concentrations were similar for the two groups. Nine (12.7%) first season and 8 (12.7%) second season subjects experienced one or more serious adverse events; most were respiratory and all were considered to be not or probably not related to palivizumab. No deaths occurred during the study. CONCLUSIONS: Monthly palivizumab injections were not associated with adverse immune responses or adverse events in young children receiving palivizumab for one or two seasons. Children receiving palivizumab for a second season did not experience more severe adverse events than those receiving it for the first time.

Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV.

Palivizumab (Synagis; Abbott Laboratories), a humanized, monoclonal antibody, prevents lower respiratory tract infection by respiratory syncytial virus (RSV). RSV causes significant morbidity and mortality in young children worldwide and is particularly severe in pre-term infants, children with cardiopulmonary disease, and the immunosuppressed population. The first such genetically engineered agent to be used effectively against a human infectious disease, palivizumab significantly reduces the number of hospitalizations caused by RSV in high-risk infants. This article reviews the preclinical development and clinical experience of palivizumab.

Prevention of respiratory syncytial virus infections in high-risk infants by monoclonal antibody (palivizumab).

Respiratory syncytial virus (RSV) is a major viral pathogen which causes serious respiratory illness in infants and children worldwide. Palivizumab (Synagis) is an anti-RSV monoclonal antibody administered intramuscularly for the prevention of severe RSV respiratory disease in high-risk infants and young children. The IMpact-RSV trial, the pivotal multicenter, randomized, placebo-controlled trial performed in the USA, Canada and the United Kingdom demonstrated an overall 55% reduction in hospitalization rate due to RSV infection in preterm infants (< or = 35 weeks gestation) with and without chronic lung disease (CLD). Subgroup analysis in premature infants without CLD revealed an even greater reduction in RSV hospitalization rates (78%). Adverse events were infrequent and did not differ between placebo and palivizumab groups. Injection site reactions were infrequent and mild; no differences were observed between palivizumab and placebo subjects. Palivizumab does not interfere with administration of other pediatric vaccines. Comprehensive parent education programs regarding prevention of infection, avoidance of risk factors for infection, careful adherence to infection control policies, and recognition of early symptoms of RSV infection remain important components of RSV prevention strategies. In light of the lack of effective vaccines for this serious health risk, palivizumab offers the only option for prophylaxis against RSV disease in high-risk infants.