Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada.

PURPOSE: To determine the outcomes in children at high risk for death or complications from respiratory disease who are hospitalized with respiratory syncytial virus (RSV) infection. DESIGN: Retrospective chart review. SETTING: Twelve pediatric tertiary care centers. PATIENTS: All hospitalized children with an RSV infection diagnosed by a positive antigen detection test result or viral isolation during the study period from 1988 to 1991, encompassing three winter seasons. Charts from patients in the following high-risk groups were reviewed in detail: (1) congenital heart disease, (2) chronic lung disease, (3) immunodeficiency, (4) age less than 6 weeks, (5) gestational age less than 36 weeks, and (6) hypoxia (defined as oxygen saturation less than 90% or arterial oxygen pressure less than 60 mm Hg). MEASUREMENTS: The age of all children, the date of RSV identification, and the use of oxygen supplementation, intensive care, and ventilatory support. In addition, the duration of these treatments and the duration of hospitalization were noted. Left-to-right shunting and pulmonary hypertension before RSV infection were determined in those children with congenital heart disease. The nature of the chronic lung disease was noted. Death within 2 weeks of RSV identification was recorded, and the use of ribavirin, bronchodilators, and corticosteroids was determined. RESULTS: Significant year-to-year variation in the frequency of RSV infection was confirmed, with a peak during the 1989-1990 winter noted by the majority of centers (p = 0.0001). Of the 1584 patients in the study, 260 had underlying cardiac disease, 200 had chronic lung disease, 35 had compromised immune function, 378 had been premature, 373 were less than 6 weeks of age, and 338 had hypoxia. Seventeen patients died within 2 weeks (mortality rate 1%); significantly more patients with underlying cardiac disease (3.4%) or lung disease (3.5%) died. Immunocompromised patients had the longest hospital stay (median 39 days), followed by those patients with underlying cardiac or pulmonary disease (11 days); patients less than 6 weeks of age (5 days) and those with hypoxia (6 days) had the shortest hospital stays. Patients with underlying cardiac and pulmonary disease also required oxygen supplementation for a significantly longer period. CONCLUSION: The year-to-year variation in frequency of RSV infection was confirmed in this study. Morbidity and mortality rates associated with RSV infection in a high-risk population in Canada were significantly lower than previously reported.     

Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease: a review of the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada.

OBJECTIVE: We wished to compare outcomes of respiratory syncytial virus (RSV) infection in children with bronchopulmonary dysplasia (BPD) with those with other pulmonary disorders: cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, and tracheoesophageal fistula. METHODS: Children with RSV infection hospitalized at seven Canadian pediatric tertiary care hospitals in 1993 through 1994 and 9 hospitals in 1994 through 1995 were enrolled and prospectively followed. This study is a secondary analysis of data from this prospective cohort. RESULTS: Of the 1516 patients enrolled the outcomes of 159 with preexisting lung disorders before RSV lower respiratory tract infection constitute this report. There were no significant differences among the 7 groups (BPD, cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, tracheoesophageal fistula, other) for the morbidity measures: duration of hospitalization, intensive care unit (ICU) admission, duration of ICU stay, mechanical ventilation and duration of mechanical ventilation. Patients using home oxygen were more likely to be admitted to the ICU than those who had never or previously used home oxygen (current 57.1%, past 23.8%, never 33.3%, P = 0.03). CONCLUSIONS: Children with other underlying diseases have morbidity similar to those with BPD. Prophylactic interventions against RSV should also be studied in these groups.     

The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation

BACKGROUND: Infants born at 33 through 35 completed weeks of gestation (33-35GA) are at risk for severe respiratory syncytial virus (RSV) infection, and palivizumab prophylaxis lowers hospitalizations for RSV infection by as much as 80%. The 33-35GA cohort comprises 3-5% of annual births; thus expert panels recommend limiting prophylaxis to situations in which frequency or health care impact of RSV infection is high. This study sought to identify independent risk factors for hospitalization for RSV infection. METHODS: This was a multicenter, prospective, observational cohort study of 33-35GA infants followed through their first RSV season (2001/2002 or 2002/2003). Baseline data were collected by interview with parents and review of medical records. Respiratory tract illnesses were identified by monthly phone calls, and medical records were reviewed for emergency room visits or hospitalizations. Risk factors were determined by stepwise logistic regression. RESULTS: Of 1,860 enrolled subjects, 1,832 (98.5%) were followed for at least 1 month, and 1,760 (94.6%) completed all follow-ups. Of 140 (7.6%) subjects hospitalized for respiratory tract illnesses, 66 infants had proven RSV infection. Independent predictors for hospitalization for RSV infection were: day-care attendance (odds ratio, 12.32; 95% confidence interval, 2.56, 59.34); November through January birth (odds ratio, 4.89; 95% confidence interval, 2.57, 9.29); preschool age sibling(s) (odds ratio, 2.76; 95% confidence interval, 1.51, 5.03); birth weight <10th percentile (odds ratio, 2.19; 95% confidence interval, 1.14, 4.22); male gender (odds ratio, 1.91; 95% confidence interval, 1.10, 3.31); > or = 2 smokers in the home (odds ratio, 1.87; 95% confidence interval, 1.07, 3.26); and households with >5 people, counting the subject (odds ratio, 1.79; 95% confidence interval, 1.02, 3.16). Family history of eczema (odds ratio, 0.42; 95% confidence interval, 0.18, 0.996) was protective. CONCLUSIONS: Specific host/environmental factors can be used to identify which 33-35GA infants are at greatest risk of hospitalization for RSV infection and likely to benefit from palivizumab prophylaxis.     

The Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of neonatal group B streptococcal infections in Canada

OBJECTIVES:

To determine the presentation and medical outcomes of neonatal group B streptococcus (GBS) disease in Canada, and describe maternal and obstetrical risk factors.

DESIGN:

Retrospective review of health records and laboratory databases using standardized data collection forms.

SETTING:

All neonates diagnosed with GBS infections in 1992 at 13 Canadian paediatric centres.

RESULTS:

A total of 105 infants meeting the criteria for neonatal GBS disease were identified. The majority of cases (78 or 74.3%) had early-onset disease (EOD); 78.9% (60 of 76) of these cases presented within 24 h of delivery. Rates of EOD (less than seven days) varied from 0.44/1000 live births to 2.1/1000 live births, with an overall rate of 1.2/1000 live births. Pneumonia was the most common clinical illness (43.8%), followed by bacteremia without focus (23.8%) and meningitis (16.2%). At least one maternal risk factor for neonatal GBS disease was noted in 46 of 78 (59%) infants with EOD. A median of one dose (range one to 23 doses) of intrapartum antibiotics was given in 18 of 75 (24%) of the pregnancies. Overall, the mean gestational age at birth was 36.2±4.7 weeks, with 38 of 96 (39.6%) infants having a gestational age at birth younger than 37 weeks (31 of 73 [42.5%] EOD cases were born with a gestational age younger than 37 weeks). The median birth weight was 3099 g (range 610 g to 4830 g). Thirty of 94 (31.9%) infants had a birth weight less than 2500 g. Seventeen (16.2%) infants died.

CONCLUSIONS:

In 1992, neonatal GBS disease was a significant cause of morbidity and mortality in Canadian infants. More than half of the cases identified in this study could have been potentially preventable by the use of intrapartum antibiotics for women with known risk factors. There is a need for prospective studies to better define risk factors and preventative measures for neonatal GBS infections in Canada.     

Nosocomial respiratory syncytial virus infection in neonatal units in the United Kingdom

Nosocomial Respiratory Syncytial Virus infections are frequently reported and tend to be more severe, because of comorbidity, such reports, however, are frequently from a single centre. The incidence and outcomes of nosocomial Respiratory Syncytial Virus infection in UK neonatal units over a five year period were estimated by interrogating the Capse Health Care Knowledge Systems database, which contains anonymised details of 55% of UK hospital admissions. A total of 79,642 admissions commenced on the infants' date of birth and contained an ICD-10 code for low birth weight or immaturity. Thirty-seven of the 79,642 admissions also contained a Respiratory Syncytial Virus code. Two (5.4%) with Respiratory Syncytial Virus and 2,736 (3.4%) without Respiratory Syncytial Virus died. Survivors with Respiratory Syncytial Virus codes experienced significantly increased length of stay. In the extreme immaturity sub-group the length of stay was 117.5 days with Respiratory Syncytial Virus and 51.3 days without Respiratory Syncytial Virus (p = 0.0002). In the low birth weight or other preterm sub-group the length of stay with Respiratory Syncytial Virus was 69.2 and without Respiratory Syncytial Virus 14.7 days (p < 0.0001). The observed low rate for nosocomial Respiratory Syncytial Virus (0.46/1000 admissions) should be regarded as a minimum. The increased length of stay in infants with Respiratory Syncytial Virus infection emphasises that units should have guidelines to prevent and deal with Respiratory Syncytial Virus outbreaks.     

Nosocomial respiratory syncytial virus infection in neonatal units in the United Kingdom

Nosocomial Respiratory Syncytial Virus infections are frequently reported and tend to be more severe, because of comorbidity, such reports, however, are frequently from a single centre. The incidence and outcomes of nosocomial Respiratory Syncytial Virus infection in UK neonatal units over a five year period were estimated by interrogating the Capse Health Care Knowledge Systems database, which contains anonymised details of 55% of UK hospital admissions. A total of 79,642 admissions commenced on the infants' date of birth and contained an ICD-10 code for low birth weight or immaturity. Thirty-seven of the 79,642 admissions also contained a Respiratory Syncytial Virus code. Two (5.4%) with Respiratory Syncytial Virus and 2,736 (3.4%) without Respiratory Syncytial Virus died. Survivors with Respiratory Syncytial Virus codes experienced significantly increased length of stay. In the extreme immaturity sub-group the length of stay was 117.5 days with Respiratory Syncytial Virus and 51.3 days without Respiratory Syncytial Virus ( p = 0.0002). In the low birth weight or other preterm sub-group the length of stay with Respiratory Syncytial Virus was 69.2 and without Respiratory Syncytial Virus 14.7 days ( p > 0.0001). The observed low rate for nosocomial Respiratory Syncytial Virus (0.46/1000 admissions) should be regarded as a minimum. The increased length of stay in infants with Respiratory Syncytial Virus infection emphasises that units should have guidelines to prevent and deal with Respiratory Syncytial Virus outbreaks.     

Prophylaxis of respiratory syncytial virus in Canada in 2003

Passive immunization of high-risk children with the humanized monoclonal antibody palivizumab is the mainstay of respiratory syncytial virus (RSV) prophylaxis in Canada in 2003. This product appears to be safe, and it prevents the majority of RSV hospitalizations in infants born before 36 weeks gestational age, and about half in children under 24 months of age with hemodynamically significant congenital heart disease. However, the high cost of palivizumab and the fact that at least 12 infants need to be treated throughout RSV season to prevent one hospitalization make it difficult to determine the ideal indications for the product. Because these high-risk infants account for a minority of RSV hospitalizations, it is desirable to search for a prophylactic strategy that is practical to apply in all infants.     

Severe respiratory syncytial virus infection in older children

Serious respiratory syncytial virus (RSV) disease requiring hospitalization occurs primarily in infants younger than 12 months. The incidence, risk factors, and clinical features in older children have not been studied extensively. Of 282 children hospitalized at our institution with severe RSV disease during a 3-year period, 62 (22%) were older than 12 months. These 62 older children were matched for sex, onset of illness, and hospital location with 62 hospitalized children younger than 12 months with proved RSV infection. Older children had underlying chronic disease more commonly than younger children (47 of 62 vs 24 of 62). Chronic illnesses in older children included bronchopulmonary dysplasia and/or reactive airway disease (34 of 47), congenital heart disease (9 of 47), gastrointestinal disease (7 of 47), and genetic disorders (7 of 47). Three of the four deaths from RSV infection occurred in older children; all four had underlying disease (three with congenital heart disease and one with biliary atresia). We conclude that children older than 12 months with underlying disease are at increased risk for serious or fatal RSV infection and are not always protected by previous RSV disease. Such older children should be considered candidates for passive or active immunoprophylaxis against RSV infection as such agents become available.     

Palivizumab prophylaxis for respiratory syncytial virus in Canada: utilization and outcomes

OBJECTIVE: To provide information on the use and outcomes of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus (RSV) infection. DESIGN: Observational, prospective, longitudinal, multicenter study. SETTING: Eighteen hospitals and pediatric clinics located in six provinces across Canada. PATIENTS: Infants enrolled in the palivizumab Special Access Programme of Canada's Therapeutic Products Programme throughout the 1999 to 2000 RSV season. Most were premature infants born at < or = 32 weeks of gestation and/or had bronchopulmonary dysplasia. METHODS AND MAIN OUTCOME MEASURES: Neonatal and demographic data were recorded for each subject. The parent/caregiver was contacted on a monthly basis until the end of the RSV season to obtain information on palivizumab utilization and compliance as well as incidence and severity of respiratory infections. RESULTS: There were 444 evaluable subjects who each received 1 to 7 injections of palivizumab for a total of 1702 doses from September 1999 to April 2000. Most subjects received 5 injections with high compliance. Prophylaxis was discontinued in 2% of children. There were 116 clinical events or hospitalizations involving respiratory tract infections reported in 91 children. Eighty-six of these were managed in an outpatient setting, and 30 required hospitalization. The estimated incidence of hospitalization for RSV-positive lower respiratory tract infections (LRTIs) was 2.4%. Hospitalization for RSV LRTI occurred more often in children with bronchopulmonary dysplasia (6.0%) than in those with prematurity only (1.6%). CONCLUSIONS: This study demonstrates that prophylaxis with palivizumab during the RSV season was associated with a low rate of hospitalization for RSV-positive LRTIs. Palivizumab was well-tolerated, and compliance was high. The findings confirm the results of the major randomized clinical trial of palivizumab and demonstrate the safety and effectiveness of RSV prophylaxis.     

Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin

Keck M, Mindru C, Kalil AC, Mercer DF, Florescu DF. Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin. Abstract: The mainstay of therapy for RSV disease is supportive care, although aerosolized ribavirin has been used to treat infants and young children with severe lower respiratory tract infections. Aerosolized ribavirin has adverse effects, high cost and teratogenic potential. We report the case of a pediatric liver transplant recipient diagnosed with lower respiratory RSV infection, who was successfully treated with oral ribavirin.     

Nosocomial viral infections in a pediatric service: example of rotaviral gastroenteritis and respiratory syncytial viral bronchiolitis]

Nosocomial infections are a preoccupation in a pediatric hospital mainly during the winter with bronchiolitis and gastroenteritis epidemics. We have examined the risk factors of nosocomial infections. MATERIAL AND METHODS: A prospective study was conducted between November, 1999 and March, 2000 in the infants units of the Le Havre hospital. We systematically listed the admissions and contacted the family after their discharge by phone. A geographic information system was implemented to display the epidemiological data; this software is able to illustrate the sectors at risk. RESULTS: During the study, 687 infants were hospitalized of whom 458 for bronchiolitis and community-acquired gastroenteritis. Mean age was 5.4 months old. No nosocomial bronchiolitis occurred. Prevalence of nosocomial gastroenteritis was 10% (68 cases including nine after discharge). Infants with nosocomial infection were younger than those with community-acquired infection (6.6 months vs. 11.2 months, P < 0.01). The mean length of stay was longer in nosocomial infection (7.7 vs. 4.1 days, P < 0.05). Among the infants with bronchiolitis, 16% have developed nosocomial intestinal infections (RR = 2.65, IC: 1.59-4.4; P < 0.01). The geographic analysis pointed the area with nosocomial risk (bedroom without water, nearness of nurse office and games room). CONCLUSION: Geographic information system is a part of the quality control system and may have some interaction effect on final decision making. Incidence of nosocomial infections showed the need for a prevention strategy in a pediatric hospital.     

Burden of respiratory syncytial virus infection in young children

Respiratory syncytial virus (RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants (below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-risk infants, lowers the burden of RSV infection in certain carefully selected patient groups.     

Clinical predictors of respiratory syncytial virus infection in children

Aim: The aim of this study was to develop a clinical prediction model that identifies respiratory syncytial virus (RSV) infection in infants and young children.
Methods: Children ≤ 36 months of age with respiratory illness, who were suspected of having RSV infection, were enrolled in this prospective cohort study during the study period between January and February 2002. RSV testing was performed on all patients.
Results: Of the 197 patients enrolled in the study, 126 (64%) were positive for RSV and 71 (36%) patients were either negative for RSV or had a positive culture for viruses other than RSV. The mean age of patients was 5 months and 57% were male. Backwards stepwise logistic regression analysis identified cough (p = 0.000), wheezing (p = 0.002), and retractions (p = 0.008) as independent variables predictive of RSV infection. The prediction model had a sensitivity of 80% (95% CI, 71–87%), specificity of 68% (95% CI, 54–79%), positive predictive value 82% (95% CI, 74–89%), negative predictive value 66% (95% CI, 52–77), positive likelihood ratio 2.5 (95% CI, 1.8–3.7) and post-test probability of 82%.
Conclusion: The combination of cough, wheezing and retractions predicts RSV infection in infants and young children.