Respiratory Syncytial Virus Testing Research Articles

Host and Viral Factors Affecting Clinical Performance of a Rapid Diagnostic Test for Respiratory Syncytial Virus in Hospitalized Children

Respiratory syncytial virus rapid antigen detection tests (RADT) are used widely. RADT exhibited high specificity (97%) and moderate sensitivity (80%) compared with reverse-transcriptase polymerase chain reaction in 720 hospitalized children <3 years old. Older age, prolonged symptoms, and respiratory syncytial virus genotype-B infection were significantly associated with false-negative results of RADT.

Bronchiolite et prise alimentaire des dernières 24 h : un outil de dépistage de l’hypoxie

BackgroundHypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24h (bottle and spoon feeding), as a percentage of usual intake (24h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs. MethodsIn this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6months, with bronchiolitis (rhinorrhea+dyspnea+cough+expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2) was recorded. Hypoxia was noted if SpO2 was below 95% and verified. Results24h FI greater or equal to 50% was associated with a 96% likelihood of SpO2 greater or equal to 95% [95% CI, 91–99%]. In univariate analysis, 24h FI less than 50% had the highest odds ratio (13.8) for SpO2 less than 95%, compared to other 24h FI values and other clinical signs, as well as providing one of the best compromises between specificity (90%) and sensitivity (60%) for identifying infants with hypoxia. In multivariate analysis with adjustment for age, SpO2 less than 95% was related to the presence of intercostal retractions (OR=9.1 [95% CI, 2.4–33.8%]) and 24h FI less than 50% (OR=10.9 [95% CI, 3.0–39.1%]). Hospitalization (17 infants) was strongly related to younger age, 24h FI and intercostal retractions. ConclusionIn practice, the measure of 24h FI may be useful in identifying hypoxia and deserves further study.

Rapid Antigen-Based Testing for Respiratory Syncytial Virus: Moving Diagnostics from Bench to Bedside?

Respiratory syncytial virus (RSV) is the most important cause of infantile bronchiolitis and pneumonia. It is ubiquitous, with most children acquiring their primary infection within the first year of life and with subsequent reinfection occurring in all age groups. Clinically, RSV is virtually indistinguishable from other viral respiratory infections. Traditionally, the microbiologic diagnosis of RSV has been based on moderate to complex techniques performed in a laboratory (cell culture, nucleic acid amplification and immunofluorescence assays); however, rapid antigen-detection tests offer potential advantages associated with point-of-care testing. This review seeks to familiarize the readers with RSV rapid antigen-detection tests, describe their performance characteristics and comment on their strengths and weaknesses. The authors will discuss the impact of rapid RSV testing on clinical practice, with a look to the future of what the field ultimately requires of a point-of-care diagnostic technique.

Food intake during the previous 24 h as a percentage of usual intake: a marker of hypoxia in infants with bronchiolitis: an observational, prospective, multicenter study

BackgroundHypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24 hours (bottle and spoon feeding), as a percentage of usual intake (24h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs.MethodsIn this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea + dyspnea + cough + expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded.The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2) was recorded. Hypoxia was noted if SpO2 was below 95% and verified.Results24h FI ≥ 50% was associated with a 96% likelihood of SpO2 ≥ 95% [95% CI, 91–99]. In univariate analysis, 24h FI < 50% had the highest odds ratio (13.8) for SpO2 < 95%, compared to other 24h FI values and other clinical signs, as well as providing one of the best compromises between specificity (90%) and sensitivity (60%) for identifying infants with hypoxia. In multivariate analysis with adjustment for age, SpO2 < 95% was related to the presence of intercostal retractions (OR = 9.1 [95% CI, 2.4-33.8%]) and 24h FI < 50% (OR = 10.9 [95% CI, 3.0-39.1%]). Hospitalization (17 infants) was strongly related to younger age, 24h FI and intercostal retractions.ConclusionIn practice, the measure of 24 h FI may be useful in identifying hypoxia and deserves further study.

Comparative Evaluation of the Nanosphere Verigene RV+ Assay and the Simplexa Flu A/B &amp; RSV Kit for Detection of Influenza and Respiratory Syncytial Viruses

Using retrospective (n = 200) and prospective (n = 150) nasopharyngeal specimens, we evaluated the Nanosphere Verigene RV+ and the Focus Diagnostics Simplexa Flu A/B & RSV tests. Overall, RV+ demonstrated sensitivities and specificities of 96.6% and 100% for influenza A virus, 100% and 99.7% for influenza B virus, and 100% and 100% for respiratory syncytial virus (RSV), while the Simplexa test sensitivities and specificities were 82.8 and 99.7%, 76.2 and 100%, and 94.6 and 100%, respectively.

Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis.

BackgroundEvidence on the effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis with palivizumab in children with cystic fibrosis (CF) is lacking.MethodsWe utilized Medicaid Extract files from 27 states from 1999 to 2006 linked to the National Cystic Fibrosis Registry to establish a cohort of children 0–2 years with CF diagnosis. Eligible children entered the cohort after CF diagnosis and after RSV season onset, and were followed until season end, second birthday, death, or hospitalizations for reasons other then the study outcome. Two outcomes were examined: hospitalization for RSV infections (RSV‐ha), or hospitalization for acute respiratory infections (ARI‐ha). Palivizumab exposure was defined based on pharmacy or procedure claims as current (claim date plus 30 days), former (day 31–60 after a claim), and no exposure (days before the first or >60 days after any claim). Both outcomes were examined in a Cox regression model, adjusting for RSV risk factors and CF severity via exposure propensity score.ResultsThe matched cohort included 1,974 infants (2,875 infant seasons), who experienced 32 RSV‐ha and 212 ARI‐ha (3.9 and 26.2/1,000 season months, respectively). Compared to periods of no use, the adjusted hazard ratio for current use was 0.57 (95% confidence interval [CI]: 0.20–1.60) for RSV‐related hospitalization and 0.85 (95% CI: 0.59–1.21) for ARI‐related hospitalization. Each month of increasing age reduced the ARI‐ha by 5.8%.ConclusionRSV hospitalization incidence was low suggesting either little contribution of the virus to respiratory infections in patients with CF or lack of RSV testing. Unadjusted and adjusted RSV‐hospitalization incidence rates suggested potentially positive effects of palivizumab, but results were inconclusive due to small event rates. Hospitalizations for acute respiratory illness with possible RSV contribution showed no association with palivizumab use, suggesting limited overall effect of palivizumab. Younger age greatly increased infection risk. Pediatr Pulmonol. 2013; 48:874–884. © 2012 Wiley Periodicals, Inc.

418 Usefulness of Rapid Test for Respiratory Syncytial Virus(RSV) in the Diagnosis of Lower Respiratory Tract Infections in 0–3Years Old Children1

IntroductionLower respiratory tract infections caused by RSV in form of bronchitis or bronchiolitis are the main reasons of hospitalization in infancy and early childhood.AimThe aim of the study was to...

Deciphering the Importance of Host and Environmental Factors that Influence the Genesis of Asthma During Childhood

Deciphering the Importance of Host and Environmental Factors that Influence the Genesis of Asthma During Childhood

A thin layer-based amperometric enzyme immunoassay for the rapid and sensitive diagnosis of respiratory syncytial virus infections

A simple electrochemical sandwich immunoassay involving a polystyrene microarray slide coated with monoclonal capture antibodies and carbon screen-printed sensors (SPS) was designed for the rapid diagnosis of respiratory syncytial virus (RSV). The detection of the antibody-antigen complex formation relied on the use of a horseradish peroxidase conjugate. Its chronoamperometric measurement detection was performed by confining a droplet of H2O2/3,3',5,5'-tetramethylbenzidine enzyme substrate/mediator solution within a thin layer between one spot of the microarray and the surface of one screen-printed electrochemical cell. The accumulation of the enzyme product in the thin film of liquid enhanced the electrochemical response which allowed the development of a rapid (25min) and sensitive thin layer-based amperometric (TLA) enzyme immunoassay. The method was successfully compared to commercially-available immunofluorescent and real-time PCR assays for RSV testing in respiratory secretion clinical samples. This suggests that owing to its rapidity, convenience, low-cost, portability and ability to provide quantified results, the reported concept could be a promising point-of-care diagnostic tool to screen patients with suspected respiratory infection or other types of infectious diseases.

Chronic Diseases, Chromosomal Abnormalities, and Congenital Malformations as Risk Factors for Respiratory Syncytial Virus Hospitalization: A Population-Based Cohort Study

Little is known about how chronic conditions other than prematurity, heart disease, and Down syndrome affect the risk and severity of hospitalization for respiratory syncytial virus (RSV). We assess the risk and severity of RSV hospitalization in children with chronic conditions in this register-based, population-based cohort study. Data on RSV tests, maternal smoking, siblings, single parenthood, mode of delivery, gestational age at birth, major surgery, asthma diagnosis, chronic conditions, and hospitalization and discharge dates were obtained from the Danish RSV database, the National Patient and Birth Registries, and the Civil Registration System. Cox regression models were used to estimate incidence rate ratios (IRRs) for RSV hospitalization between groups stratified by sex and date of birth. Duration of RSV hospitalization was analyzed in a linear regression and reported as geometric mean ratios. A total of 391 983 children aged 0-23 months were included in the analysis. A total of 10,616 (2.7%) had a diagnosis for chronic disease. IRRs (95% confidence intervals) for RSV hospitalization in children with any congenital or acquired chronic condition were 2.18 (2.01-2.36) and 2.25 (1.94-2.61), respectively. Several new risk factors for RSV hospitalization, including malformations, interstitial lung disease, neuromuscular disease, liver disease, chromosomal abnormalities, congenital immunodeficiencies, and inborn errors of metabolism, were identified. Duration of RSV hospitalization was increased in many chronic conditions. Chronic disease per se is an important risk factor for RSV hospitalization.

High incidence of respiratory viruses in critically ill children

Background: Acute lower respiratory tract illness is a major cause of hospitalization, respiratory failure, and death in children worldwide. However, infectious agents are not identified in >50% of these clinical illnesses using traditional methods such as rapid antigen detection assays or viral culture. Objective: To conduct a pilot study using RT-PCR to determine the frequency of respiratory viruses in critically ill children with respiratory compromise. Methods: Critically ill children admitted to the Pediatric Critical Care Unit during 2 winter seasons with respiratory compromise or failure were prospectively enrolled. Respiratory tract specimens (tracheal lavage or nasal wash) were tested for 11 different viruses using realtime RT-PCR, including respiratory syncytial virus (RSV), human metapneumovirus (HMPV), influenza A (IAV) and B (IBV), parainfluenza viruses (PIV) 1-3, coronaviruses OC43, 229E, and Netherlands, and human rhinovirus (HRV). Results: Thirty-two children were enrolled, 28 (88%) of which required mechanical ventilation. Clinical diagnoses included bronchiolitis, croup, asthma, apnea, and pneumonia. Of these patients, 28/32 (88%) tested positive for one of eleven viruses by RT-PCR. Compared to antigen testing for RSV, IAV, and IBV, RT-PCR detected an additional nine infections for an increased yield of 53%. RT-PCR also detected coronavirus infections in five patients, including three patients with Netherlands coronavirus. Co-infection with more than one virus was detected in 8/32 (25%). None of the 32 patients tested positive for HMPV, PIV 1, or PIV 3. Conclusions: We detected a respiratory virus in 88% of children with respiratory failure. RT-PCR significantly increased the identification of viruses compared to antigen testing. RSV, influenza A, and coronaviruses were the most common viruses detected. Our data suggest that a viral etiology can be identified in the majority of childhood episodes of severe respiratory disease and that RT-PCR is a useful addition to the diagnostic approach.

CARESS: The Canadian Registry of Palivizumab

Palivizumab is indicated for respiratory syncytial virus (RSV) prophylaxis in high-risk children. However, relatively little is known about the current use, compliance, and outcomes associated with this medication. A prospective, observational, registry based on 27 sites, with monthly follow-up of infants at high risk for RSV who received at least 1 dose of palivizumab during the 2005-2009 RSV seasons. A total of 5286 children were enrolled (56.6% male; 71.7% white; average gestational age, 32.1 ± 5.5 weeks). Of them, 3741 patients (70.8%) were prophylaxed for prematurity only, 449 (8.5%) for bronchopulmonary dysplasia/chronic lung disease, 508 (9.6%) for congenital heart disease, and 588 (11.1%) for other reasons. Overall, 19,485 doses were given. On average, infants received 86.0% ± 28.4% of their expected number of injections; 71.2% of infants received their injections in the recommended time periods. Of the 5286 participants enrolled, 308 patients were hospitalized for respiratory tract illness (hospitalization rate, 5.8%). The RSV-hospitalization rate was calculated as 1.38%. Having siblings increased likelihood of hospitalization (66.9% vs. 55.7%, P < 0.005), and was significantly correlated with time to hospitalization in this cohort (P = 0.050). The overall RSV-hospitalization rate in our study was within the range found in previous reports (1.3%-5.3%), although it did not mimic the declining rates of the US Palivizumab Outcomes Registry. This could be due to increased testing for RSV when hospitalized and increasing rates of prophylaxis of infants with underlying medical disorders.

Paediatric intensive care admissions for respiratory syncytial virus bronchiolitis in France: results of a retrospective survey and evaluation of the validity of a medical information system programme

The purpose of this study was to describe the characteristics of patients with bronchiolitis admitted to a paediatric intensive care unit (PICU), and to evaluate a national registry of hospitalizations (Programme de Médicalisation des Systèmes d'Information; PMSI) as a potential source of epidemiological data. Of the 49 French PICUs invited to take part in a retrospective survey of children aged <2 years who were hospitalized during the 2005-2006 epidemic season, 24 agreed to participate. Overall, 467 children were enrolled: 75% were aged <2 months, 76% had positive respiratory syncytial virus (RSV) tests, 34·9% required non-invasive ventilation, 36·6% were mechanically ventilated, and six infants died. The main neonatal characteristics were: prematurity (31·9%), respiratory disease (16·5%), congenital heart disease (6·4%), receiving mechanical ventilation (11·6%), and bronchopulmonary dysplasia at day 28 (3·8%). For bronchiolitis episode, the kappa coefficient between the survey and PMSI data was good only for mechanical ventilation (0·63) and the death rate (0·86).

Frequent Detection of Respiratory Viruses without Symptoms: Toward Defining Clinically Relevant Cutoff Values

Highly sensitive techniques, such as PCR, have greatly improved the detection of respiratory viruses. However, the sensitivity of PCR tests also complicates clinical interpretation, as the presence of small amounts of viral targets may not necessarily have clinical relevance. We performed a prospective case-control study in asymptomatic and symptomatic young children. PCR detection of 14 respiratory viruses was performed in nasal washes, and results were quantified in copies per milliliter. A total of 141 cases and 157 controls were included. In 72% of the cases and 28% of the controls, at least one virus was identified. When stratified for age, at least one virus was identified in 47% of the controls younger than 1 year old. Rhinovirus (RV) was frequently detected in both symptomatic and asymptomatic individuals. Receiver operating characteristic analysis for quantitative rhinovirus detection showed that cutoff values for clinical relevance are feasible for RV. In contrast to rhinovirus, respiratory syncytial virus (RSV) was rarely detected in controls, suggesting that a positive RSV test result is almost always of clinical relevance, independent of viral quantity. In conclusion, our study shows that asymptomatic carriage of a respiratory virus occurs frequently in young children. However, significant differences in the amount of virus present were observed between cases and controls. This suggests that defining cutoff levels should be feasible and represents the next necessary step for diagnosing viral respiratory infections using molecular tests.

Modeling the variations in pediatric respiratory syncytial virus seasonal epidemics.

BackgroundSeasonal respiratory syncytial virus (RSV) epidemics occur annually in temperate climates and result in significant pediatric morbidity and increased health care costs. Although RSV epidemics generally occur between October and April, the size and timing vary across epidemic seasons and are difficult to predict accurately. Prediction of epidemic characteristics would support management of resources and treatment.MethodsThe goals of this research were to examine the empirical relationships among early exponential growth rate, total epidemic size, and timing, and the utility of specific parameters in compartmental models of transmission in accounting for variation among seasonal RSV epidemic curves. RSV testing data from Primary Children's Medical Center were collected on children under two years of age (July 2001-June 2008). Simple linear regression was used explore the relationship between three epidemic characteristics (final epidemic size, days to peak, and epidemic length) and exponential growth calculated from four weeks of daily case data. A compartmental model of transmission was fit to the data and parameter estimated used to help describe the variation among seasonal RSV epidemic curves.ResultsThe regression results indicated that exponential growth was correlated to epidemic characteristics. The transmission modeling results indicated that start time for the epidemic and the transmission parameter co-varied with the epidemic season.ConclusionsThe conclusions were that exponential growth was somewhat empirically related to seasonal epidemic characteristics and that variation in epidemic start date as well as the transmission parameter over epidemic years could explain variation in seasonal epidemic size. These relationships are useful for public health, health care providers, and infectious disease researchers.

Comparison of human metapneumovirus and respiratory syncytial virus in children admitted to a paediatric intensive care unit

To describe the clinical presentation and course of children admitted to the paediatric intensive care unit (PICU) with human metapneumovirus (hMPV) infection, and compare them with children admitted to the PICU with respiratory syncytial virus (RSV) infection. hMPV was identified by immunofluorescence in 22 children admitted to the PICU over a 16-month period. The medical records of these children were reviewed retrospectively, and their clinical and laboratory data were compared with 66 children admitted to the PICU with positive tests for RSV over the same period. Children admitted to the PICU with hMPV were significantly older than children with RSV (P= 0.003). Children with hMPV presented more commonly with pneumonia or pneumonitis (29% vs. 16%), and less commonly with bronchiolitis (43% vs. 68%) than RSV (P= 0.13). Invasive ventilation was required in 10 patients (48%) with hMPV, and non-invasive ventilation was required in a further 5 (28%), similar to patients with RSV. Children with hMPV were more likely to have an underlying co-morbidity (P= 0.11). Children admitted to the PICU with hMPV have a similar disease presentation and severity as children admitted with RSV, including some with extremely severe disease who require additional ventilatory or cardiovascular support. Children with hMPV are likely to be older than those with RSV, and more likely to present with pneumonia and less likely to present with bronchiolitis.

Real-time PCR-based detection of Bordetella pertussis and Bordetella parapertussis in an Irish paediatric population

Novel real-time PCR assays targeting the Bordetella pertussis insertion sequence IS481, the toxin promoter region and Bordetella parapertussis insertion sequence IS1001 were designed. PCR assays were capable of detecting ≤10 copies of target DNA per reaction, with an amplification efficiency of ≥90 %. From September 2003 to December 2009, per-nasal swabs and nasopharyngeal aspirates submitted for B. pertussis culture from patients ≤1 month to >15 years of age were examined by real-time PCR. Among 1324 patients, 76 (5.7 %) were B. pertussis culture positive and 145 (10.95 %) were B. pertussis PCR positive. Of the B. pertussis PCR-positive patients, 117 (81 %) were aged 6 months or less. A total of 1548 samples were examined, of which 87 (5.6 %) were culture positive for B. pertussis and 169 (10.92 %) were B. pertussis PCR positive. All culture-positive samples were PCR positive. Seven specimens (0.5 %) were B. parapertussis culture positive and 10 (0.8 %) were B. parapertussis PCR positive, with all culture-positive samples yielding PCR-positive results. A review of patient laboratory records showed that of the 1324 patients tested for pertussis 555 (42 %) had samples referred for respiratory syncytial virus (RSV) testing and 165 (30 %) were positive, as compared to 19.4 % of the total 5719 patients tested for RSV in this period. Analysis of the age distribution of RSV-positive patients identified that 129 (78 %) were aged 6 months or less, similar to the incidence observed for pertussis in that patient age group. In conclusion, the introduction of the real-time PCR assays for the routine detection of B. pertussis resulted in a 91 % increase in the detection of the organism as compared to microbiological culture. The incidence of infection with B. parapertussis is low while the incidence of RSV infection in infants suspected of having pertussis is high, with a similar age distribution to B. pertussis infection.

Correlation between clinical and chest ultrasound findings in infants with bronchiolitis: A preliminary study

The chest ultrasound (CU) of bronchiolitis (B) in infants can reveal under thepleura focal or diffuse interstitial infiltrations (Ii)with/without minimal alveolar consolidations or microatelectasis (CA), pleural effusions, and pneumothorax. The purpose of the study has been to correlate CU findings to severity of clinical manifestations in infants with B. The study was conducted on infants hospitalized for B in our Pediatric Unit. Clinical severity of B was classified in mild, moderate and severe stages. CU features were distinguished in two categories: with/without CA. CU was executed by means of 10–12 MHz lineararray transducer in supine and prone position. Correlations were analyzed by using Fisher's exact test and Mann–Whitney test. Twenty-five infants were enrolled (11 males, median age: 4.0 months). Clinically 44% had mild B, 40% moderate and 16% severe. 78% of infants were positive to Respiratory Syncytial Virus test and 8% were normal at CU. Diffuse interstitial infiltrations were present in 82% (18% with CA) of patients with mild B, in 90% (70% with CA) with moderate B and in the totality of severe B (75%with CA). 8% hadminimal pleural effusion, none had pneumothorax. CAs were well correlated (p<0.001) to some clinical findings (moderate–severe stage, crackles, difficult to feed),moreover the timeof hospital dischargewas longer in B with CA (p<0.01). Alveolar consolidations or microatelectasis with diffuse interstitial infiltrations are most frequently associated to more severe clinical forms of B in infants.

A baby with a cough

A 12 week old baby boy of South East Asian ethnicity was admitted in winter with a three day history of cough, coryza, rapid breathing, and reduced feeding. The initial diagnosis was bronchiolitis. He deteriorated on the second day after admission with worsening respiratory distress. Testing for respiratory syncytial virus in his nasopharyngeal aspirate was negative, and he had normal inflammatory markers and white blood cell count. A chest radiograph was taken (fig 1⇓). He was started on intravenous amoxicillin because pneumonia was suspected. Fig 1 Day 1 Two days later he developed high grade fever and needed oxygen. While taking a history from his parents, they explained that the boy’s grandmother, who had looked after him since the first week of life, was visiting from Pakistan and was being investigated for chronic cough. (1) Fig 1⇑ shows an anteroposterior chest radiograph. The abnormalities are a …

Rapid testing for respiratory syncytial virus in a paediatric emergency department: benefits for infection control and bed management

Respiratory syncytial virus (RSV) is responsible for annual winter outbreaks of respiratory tract infection among children in temperate climates, placing severe pressure on hospital beds. Cohorting of affected infants has been demonstrated to be an effective strategy in reducing nosocomial transmission of RSV, and may keep cubicles free for other patients who require them. Testing of symptomatic children for RSV is standard practice, but unfortunately traditional laboratory testing is not rapid enough to aid decision-making processes. Rapid point-of-care testing (POCT) in the emergency department has been suggested as an alternative. We performed a prospective study to quantify the amount of cubicle time saved by using POCT results to allow a targeted cohorting strategy. Over the four-month study period, the POCT allowed 183 children to be admitted directly to a designated cohort area, thus saving 568.5 cubicle-days for other patients. This is equivalent to five cubicles being left free for each day of the study period. This is the first time the benefits of using POCT have been quantified in this way. POCT for RSV is a safe, cost-effective and efficient way to improve bed management.