Respiratory Syncytial Virus-associated Hospitalization Research Articles

Estimating Respiratory Syncytial Virus-associated Hospitalization in the First Year of Life Among Infants Born at 32-35 Weeks of Gestation.

Prophylaxis against respiratory syncytial virus-associated hospitalization (RSV-H) with anti-RSV monoclonal antibody is not considered cost-effective for routine use in most jurisdictions. The aim of this study was to develop a scoring tool to estimate local risk of RSV-H in the first year of life among moderately premature infants to assist in prophylaxis decision making. A retrospective cohort was constructed from population-based databases in Nova Scotia, Canada, to follow 32- to 35-week gestation infants from the prenatal period to <12 months of age, from 1998 to 2008. Potential risk factors were entered into the logistic regression model, where the dependent variable was RSV-H. Receiver operator characteristic analysis demonstrated cutoff scores producing the highest predictive accuracy, and the likelihood ratio test was used to select the final set of variables for the predictive tool. In 2811 eligible infants, the overall RSV-H rate was 3.1% (88/2811). Of 17 variables considered, 3 were used to create the scoring tool: birth during December to February, household smoke exposure and household crowding. The positive likelihood ratios of predictive tool scores for high, moderate and low of RSV-H were 3.57, 3.38 and 1.95, whereas posttest probabilities (risk of RSV-H) were 11.4%, 10.8% and 1.6%, respectively. While able to predict infants at low risk of RSV-H, the tool did not discriminate high from moderate risk infants. The tool could be used in anticipatory care to help educate families about reducing risk of serious RSV illness in their newborn.

Respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease

The purpose of this investigation was to analyze the burden of respiratory syncytial virus (RSV)-related hospitalizations in infants and children with congenital heart disease (CHD) over three consecutive RSV seasons. Retrospectively, all children with hemodynamically significant (HS-CHD) and not significant (HNS-CHD) CHD born between 2004 and 2008 at a tertiary care university hospital and identified by ICD-10 diagnoses were included. Data on RSV-related hospitalizations over the first three years of life covering at least three RSV seasons (November-April) were analyzed. The overall incidence of RSV-related hospitalization was 9.6% (58/602), without a statistically significant difference between HS-CHD and HNS-CHD (7.3% vs. 10.4%; p = 0.258). Recommendation of palivizumab prophylaxis did not influence the RSV hospitalization rates between groups. Patients with HS-CHD and early surgery were significantly less often hospitalized due to RSV compared to those with delayed surgery (1.3% vs. 14.3%; p = 0.003). The median duration of hospitalization was 8.5days (HS-CHD: 14 vs. 7days; p = 0.003). Thirteen patients (22.4%) were admitted to the intensive care unit (ICU), for a median of 10days. The median age at admission was 2months, with a significant difference between HS-CHD and HNS-CHD (6 vs. 2months; p = 0.001). The majority (97%) of RSV-related hospitalizations occurred before 12months of age. Patients with HS-CHD had a significantly more severe course of RSV disease and were older at the time of hospitalization. Early surgery seemed to significantly reduce the risk of RSV hospitalization during the first RSV season.

Respiratory Syncytial Virus-associated hospitalization in premature infants who did not receive palivizumab prophylaxis in Italy: a retrospective analysis from the Osservatorio Study.

BackgroundDue to different social and epidemiological factors, the eligibility criteria to receive palivizumab prophylaxis may be different between countries, especially in “otherwise healthy” late preterm infants.MethodsWe analyzed an Italian database of young children referred to emergency departments for acute lower respiratory tract infection (ALRI) during the RSV season over a four year period, when the use of palivizumab as prophylaxis for RSV disease was not widespread in premature infants. The demographic and environmental characteristics and the RSV positivity (RSV+) in hospitalized and not-hospitalized patients were compared. In the data analysis we divided children according to their chronologic age (age) and their week gestational age (wGA).ResultsOut of the 100 children evaluated, 68 were infants (≤12 month-age): 7.5 and 20.6 % were in the <29 and 29- < 32 wGA groups respectively, and 72.0 % in the 32- < 35 wGA group. Positive hospitalized-to-not-hospitalized ratios were found in all three wGA groups, progressively decreasing (from 4.0 to 1.2), with increasing wGA (p = 0.35). The percentage of hospitalized infants that were also RSV+ was also progressively decreasing (from 40.0 to 28.6 % and 18.4 %) with increasing wGA (p = 0.43). In the >12 month-age group (N = 32), there was positive hospitalized-to-not-hospitalized ratio only in the <29 wGA group with a low RSV+ frequency (<29 %) in all wGA groups. In the ≤12 month-age group, 41 infants were evaluated with a ≤6 month-age and 27 with a >6–12 month-age. A positive hospitalized-to-not-hospitalized ratios was found in all wGA groups in ≤6 month-age infants, despite a low RSV+ frequency in the 29- < 32 and 32- < 35 wGA group. In the >6-12 month-age group, all infants with a <29 and 29- < 32 wGA were hospitalized with a relatively high RSV+ frequency whilst the 32- < 35 wGA group showed a negative hospitalized-to-not-hospitalized ratio with a lower RSV+ frequency.ConclusionsThe hospitalized-to-not-hospitalized ratios and RSV+ frequency in the first 12 months of age in infants born prematurely confirm the vulnerability of these children for clinically important RSV infection, most notably in the <32 wGA category.

Palivizumab Effectiveness in Preventing Respiratory Syncytial Virus-Associated Hospitalization in High-Risk Infants and Children

Palivizumab Effectiveness in Preventing Respiratory Syncytial Virus-Associated Hospitalization in High-Risk Infants and Children

Respiratory Syncytial Virus-Associated Hospitalizations in Pre-Mature Infants in Lima, Peru

We conducted a prospective cohort study in four hospitals in Lima, Peru in infants with a birth weight ≤ 1,500 g followed from birth hospital discharge up to 1 year of age to determine the incidence of respiratory syncytial virus (RSV) hospitalizations. We enrolled 222 infants from March of 2009 to March of 2010: 48 infants with a birth weight < 1,000 g and 174 infants with a birth weight of 1,000-1,500 g (birth weight = 1,197 ± 224 g; gestational age = 30.1 ± 2.6 weeks). There were 936 episodes of respiratory infections; the incidence of respiratory infections during the first 1 year of life was 5.7 episodes/child-years. The incidence of RSV respiratory infections that required emergency room management was 103.9 per 1,000 child-years, and the incidence of RSV hospitalizations was 116.2 per 1,000 child-years (244.9 in infants with a birth weight < 1,000 g and 88.9 in infants 1,000-1,500 g; P < 0.05). The incidence of RSV respiratory infections that required emergency management or hospitalization is high among pre-mature infants in Lima.

Respiratory Syncytial Virus-Associated Hospitalizations Among Children Less Than 24 Months of Age

Respiratory Syncytial Virus-Associated Hospitalizations Among Children Less Than 24 Months of Age

Respiratory Syncytial Virus-associated Hospitalizations Among Infants and Young Children in the United States, 1997–2006

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease among young children in the United States. RSV-associated hospitalization increased among children in the United States during 1980 through 1996. In this study, we updated national estimates of RSV hospitalization rates among US children through 2006. We conducted a retrospective analysis of hospital discharges for lower respiratory tract illness (LRTI) in children <5 years old from the National Hospital Discharge Survey. LRTI hospitalizations were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. RSV-coded hospitalizations were International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11, 480.1, and 079.6. RSV-associated hospitalizations were the sum of RSV-coded hospitalizations and a proportion of hospitalizations coded as bronchiolitis and pneumonia during the RSV season. RSV-coded hospitalizations accounted for 24% of an estimated 5.5 million LRTI hospitalizations among children <5 years of age during the 10 study years, 1997-2006. The RSV-coded hospitalization rate in infants <1 year old was 26.0 per 1000, with no significant difference between study years. The hospitalization rate was highest among infants <3 months old (48.9 per 1000), followed by infants 3 to 5 months old (28.4 per 1000), and lower among those >1 year old (1.8 per 1000). An estimated 132,000 to 172,000 RSV-associated hospitalizations occurred annually in children <5 years of age. RSV hospitalization rates remained steady during 1997 to 2006 and were a substantial burden in the United States, especially among infants and young children. A safe and effective RSV vaccine is needed.

Development and Validation of a Risk Scoring Tool to Predict Respiratory Syncytial Virus Hospitalization in Premature Infants Born at 33 through 35 Completed Weeks of Gestation

The purpose of the study was to develop and validate a clinical instrument predicting the risk of respiratory syncytial virus (RSV)-associated hospitalization (RSV-H) in premature infants born at 33 through 35 completed weeks of gestation (33-35GA). An RSV risk scoring tool (RSV-RS) was developed by entering risk factors for RSV-H, determined in a Canadian prospective study, into a multiple logistic regression model. The scoring tool was then validated externally with data from a Spanish case-control study (FLIP). The Canadian cohort comprised 1758 RSV-positive infants born 33-35GA, of whom 66 (3.7%) had confirmed RSV-H. The FLIP data set comprised 186 (33.4%) RSV-H cases and 371 (66.7%) controls. The primary outcome measure was RSV-H. The RSV-RS score was the sum of the weighted probabilities for each included risk factor multiplied by 100 and ranged from 0 to 100. Receiver operator characteristic curve analyses determined cutoff points to predict subjects at low, moderate, or high RSV-H risk. The RSV-RS included 7 risk factors and cutoff scores of 0-48, 49-64, and 65- 100 for low-, moderate-, and high-risk subjects, respectively. For the Canadian cohort, RSV-RS sensitivity in predicting RSV-H cases was 68.2%, with 71.9% specificity. With the FLIP data set, the RSV-RS had lower accuracy (61.3% sensitivity; 65.8% specificity) but showed significant positive association with increased risk for RSV-H. The RSV-RS accurately identified 33-35GA infants at increased risk for RSV-H in a Canadian cohort. External validation with Spanish case-control study data further confirmed that the scoring tool is appropriate for the estimation of RSV-H risk.

Observational study of respiratory syncytial virus-associated hospitalizations and use of palivizumab in premature infants aged 29–32 weeks

The national observational multicenter cohort study presented here was conducted over two respiratory syncytial virus (RSV) seasons (2001–2003) in Austria to collect data on RSV-related rehospitalizations in premature infants of 29 –32-weeks’ gestational age. The results revealed an overall RSV hospitalization rate of 4.5% (36/801). Risk factors were discharge from the neonatal intensive care unit between the months of October and December, birth between June and December 2002, and neurological disease. Palivizumab prophylaxis was given to 238 (29.7%) infants, and 148 infants received inadequate or incomplete courses. Respiratory syncytial virus (RSV) infection represents a major cause of rehospitalization during the first year of life in preterm infants [1]. Recommendations for RSV prophylaxis with palivizumab [2] have been adopted without major modifications in Austria [3], and they suggest that decisions regarding this drug’s administration should be based on local epidemiological data. Currently, very limited data are available on the risk of RSV-related rehospitalization in Austria [4]. Due to the fact that insurance companies allocate and reimburse prophylaxis with palivizumab in this group of premature infants differently from published recommendations and with great local variation, we initiated a nationwide observational cohort study. The study was aimed at collecting data on RSV-related rehospitalization of premature infants of 29–32-weeks’ gestational age in order to analyze associated risk factors and to assess the use of palivizumab prophylaxis in this population. Infants were included if their gestational age was between 29 (29+0) and 32 (32+6) weeks and if they were born between 1 June 2001 and 31 December 2002. All infants were followed up until 1 June 2003. For the first RSV season, data on all rehospitalizations were collected retrospectively from medical charts and by telephone calls: for the second RSV season, which occurred after the study was initiated in February 2002, data were collected prospectively. In cases of rehospitalization due to respiratory illness, the following data were collected: patient age in months, the month in which rehospitalization occurred, severity of respiratory illness (determined using the modified clinical lower respiratory illness/infection score [5]), length of stay, number of days with supplemental oxygen, number of days at the intensive care unit, and number of days with mechanical ventilation including nasal continuous positive airway pressure. RSVantigen detection was performed on nasopharyngeal aspirates using either enzyme-linked immunosorbent assays or immunofluorescence techniques. Viral cultures were not performed. Prophylaxis with monthly administered intramuscular injections of palivizumab was usually started at the end of October or beginning of November, with the last injection in March. Recommendations for prophylaxis were influenced by local differences in allocation and reimbursement of prophylaxis by the insurance companies. Prophylaxis administration was not influenced by the study protocol. The study was approved by the local ethics committee, and informed consent was given by the parents of those infants prospectively enrolled into the study. Statistical analyses were performed using the Pearson chi-square and Yate’s corrected chi-square test, as appropriate for categorical data, and the t-test and Fisher’s exact test, as appropriate for numerical data. Multivariate analysis was performed using a logistic regression model with backward elimination and the Wald criterion. Analysis was done with SPSS (SPSS, Chicago, IL, USA), and StatXact4 (Cytel, Cambridge, MA, USA) software. B. Resch (*) . W. Gusenleitner . W. D. Muller Division of Neonatology, Department of Paediatrics, Medical University Graz, Auenbruggerplatz 30, 8036 Graz, Austria e-mail: bernhard.resch@meduni-graz.at Tel.: +43-316-3852605 Fax: +43-316-3852678

Pertussis Vaccination and the Risk of Respiratory Syncytial Virus-Associated Hospitalization

Animal data suggest an association between recent vaccination with a pertussis-containing vaccine and increased severity of respiratory syncytial virus (RSV) infection. We sought to determine whether such an association exists in humans by studying a population-based cohort of young children. We performed a nested case-control study of 280 children younger than 24 months of age hospitalized with RSV infection in Olmsted County, MN from January 1990 to December 1999. Controls (2 per case) consisted of nonhospitalized residents of Olmsted County matched to cases by date of birth and sex. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for the odds of hospitalization for RSV infection among subjects with a recent pertussis-containing vaccination in proximity to the cases' date of hospitalization relative to the odds among subjects with no vaccination. The OR for receipt of a pertussis-containing vaccine within 0 to 6 days of a case's hospitalization for RSV disease was 0.8 (95% CI 0.4-1.8). For the time intervals 7-13, 14-20 and > or =21 days, the OR were 1.3 (95% CI 0.5-3.0), 1.3 (95% CI 0.5-3.2) and 0.7 (95% CI 0.3-1.5), respectively. Adjusting for vaccine delay and for risk status did not alter the findings. The median interval between the most recent pertussis-containing vaccine and the case's date of hospitalization was 40 days for cases and 42.5 days for controls (P = 0.69). Among the RSV cases, pertussis vaccination in the month preceding hospitalization was not a risk factor for oxygen requirement (P = 0.82), intensive care unit admission (P = 0.46) or need for mechanical ventilation (P = 0.28). In our study, recent immunization with a pertussis-containing vaccine was not a risk factor for hospitalization for RSV infection. In addition, among children hospitalized with RSV infection, recent pertussis immunization was not associated with a more severe clinical course.

Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies

Objective: To determine if respiratory syncytial virus (RSV) specific, serum antibody titers correlate with protection against RSV associated-hospitalization at all ages. Design: Participants who were enrolled in a trial to determine the frequency of specific virus infections associated with hospitalization [J. Am. Med. Assoc. 283 (2000) 499] were included in our analysis if they were enrolled from July 1991 to June 1993, had a culture for virus isolation, and provided blood samples at hospitalization and 14–60 days later. RSV infection was defined by a positive culture and/or serology. Microneutralization, ELISA to the fusion (F) protein and Western blot were the serological assays that were used to determine correlates of immunity. Results: One hundred and seventy-five individuals, 1 month to 89 years old, out of 538 patients hospitalized with an acute respiratory infection met the criteria for analysis. RSV associated-hospitalization occurred in 11 (40.7%) of 27 infants (<1 year), 8 (38.1%) of 21 young children (1 to <5 years), and 15 (11.8%) of 127 children and adults (≥5 years). At the time of hospitalization, geometric mean neutralizing antibody titers (log 2) to RSV/A and RSV/B, and geometric mean binding antibody titer (log 2) to F protein were significantly higher in patients with non-RSV associated-hospitalization compared to those with RSV associated-hospitalization (RSV/A: 7.9 versus 6.1, P<0.001; RSV/B: 9.4 versus 7.3, P<0.001; ELISA-F, 13.9 versus 12.6, P=0.01). For every 1 log 2 increase in titer of neutralizing antibodies to RSV/A and RSV/B, and binding antibody to F protein there was a significant increase in the likelihood of not having an RSV associated-hospitalization by 22.3, 25, and 24.4% respectively. A minimal protective threshold titer of ≥6.0 (odds ratio 3.5; 95% CI 1.4–9.1) and ≥8.0 log 2 (odds ratio 2.9; 95% CI 1.1–7.7) against RSV associated-hospitalization was established for neutralizing antibodies to RSV/A and RSV/B; a threshold titer could not be established for binding antibody to F protein. Conclusion: Participants with naturally acquired serum neutralizing antibody levels at least equal to the minimal protective threshold titer were approximately three times more likely not to have an RSV associated-hospitalization. We speculate that achieving a minimal protective threshold antibody titer through active immunization will significantly reduce RSV associated-hospitalization among all ages.

Severity of illness models for respiratory syncytial virus-associated hospitalization.

The objective of this investigation was to examine the feasibility of multivariate severity of illness models for pediatric patients hospitalized with respiratory syncytial virus (RSV) infection. From a preexisting retrospective cohort study database, all infants and children 2 yr of age or younger with community-acquired RSV infection admitted to the University of Michigan's C. S. Mott Children's Hospital during nine epidemics were examined. The study group consisted of 802 hospitalized patients younger than 2 yr of age with community-acquired RSV infection; 182 (23%) patients had prolonged hospital length of stay defined as 7 d or greater. Multivariate logistic regression modeling of nine variables measurable during the first hospital day was strongly associated with prolonged hospitalization (p < 0.0001). Receiver operator characteristic curve analysis resulted in an area under the curve of 0.894, indicating excellent model discrimination. Goodness-of-fit testing indicated excellent model calibration for observed versus predicted outcomes (p = 0.216). We conclude that severity of illness models for RSV-associated hospitalization with excellent predictive properties in terms of classification, discrimination, and calibration are possible. Further study is required to determine if such models are generalizable across multiple centers and epidemics.