Respiratory Syncytial Virus Episode Research Articles

Substantial Burden of Nonmedically Attended RSV Infection in Healthy-Term Infants: An International Prospective Birth Cohort Study.

During the first year of life, 1 in 4 infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV therefore underrepresents the true societal burden of RSV. We assessed the burden of nonmedically attended RSV infections and compared with medically attended RSV. We performed active RSV surveillance until the age of 1 year in a cohort (n = 993) nested within the Respiratory Syncytial Virus Consortium in EUrope (RESCEU) prospective birth cohort study enrolling healthy term-born infants in 5 European countries. Symptoms, medication use, wheezing, and impact on family life were analyzed. For 97 of 120 (80.1%) nonmedically attended RSV episodes, sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97) of episodes; worries, 75.3% (73/97); anxiety, 34.0% (33/97); and work absenteeism, 10.8% (10/93). Compared with medically attended RSV (n = 102, 9 hospital admissions), Respiratory Syncytial Virus NETwork (ReSViNET) severity scores were lower (3.5 vs 4.6, P < .001), whereas duration of respiratory symptoms and was comparable. Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families, and society. These findings are important for policy makers when considering the implementation of RSV immunization. Clinical Trials Registration. ClinicalTrials.gov (NCT03627572).

Factors Predicting Secondary Respiratory Morbidity Following Early-Life Respiratory Syncytial Virus Infections: Population-Based Cohort Study.

The association between early-life respiratory syncytial virus (RSV) infections and later respiratory morbidity is well established. However, there is limited evidence on factors that influence this risk. We examined sociodemographic and perinatal factors associated with later childhood respiratory morbidity requiring secondary care following exposure to a laboratory-confirmed RSV episode in the first 2 years. We used a probabilistically linked whole-of-population-based birth cohort including 252 287 children born in Western Australia between 2000 and 2009 with follow-up to the end of 2012. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of the association of various risk factors with the first respiratory episode for asthma, wheezing, and unspecified acute lower respiratory infection beyond the age of 2 years. The analytic cohort included 4151 children with a confirmed RSV test before age 2 years. The incidence of subsequent respiratory morbidity following early-life RSV infection decreased with child age at outcome (highest incidence in 2-<4-year-olds: 41.8 per 1000 child-years; 95% CI, 37.5-46.6), increased with age at RSV infection (6-<12-month-olds: 23.6/1000 child-years; 95% CI, 19.9-27.8; 12-<24-month-olds: 22.4/1000 child-years; 95% CI, 18.2-22.7) and decreasing gestational age (50.8/1000 child-years; 95% CI, 33.5-77.2 for children born extremely preterm, <28 weeks gestation). Risk factors included age at first RSV episode (6-<12 months: aHR, 1.42; 95% CI, 1.06-1.90), extreme prematurity (<28 weeks: aHR, 2.22; 95% CI, 1.40-3.53), maternal history of asthma (aHR, 1.33; 95% CI, 1.04-1.70), and low socioeconomic index (aHR, 1.76; 95% CI, 1.03-3.00). Our results suggest that in addition to preterm and young infants, children aged 12-<24 months could also be potential target groups for RSV prevention to reduce the burden of later respiratory morbidities associated with RSV.

Economic and Clinical Outcomes of Pediatric Patients Under Two With Respiratory Syncytial Virus Infection in Thailand: A Real-world Retrospective Cohort Study.

Respiratory syncytial virus (RSV) is a common cause of acute respiratory tract infection in children, including in Thailand. We conducted this study to evaluate the economic and clinical outcomes of patients <2 years old with RSV infection at a tertiary teaching hospital in Thailand. This was a retrospective cohort study during 2014-2021. To be eligible, patients had to report at least 1 positive RSV test and were <2 years old. Descriptive statistics were used to describe baseline characteristics, healthcare resource utilization, direct medical costs (1 US dollars [USD] = 31.98 Thai Baht) and clinical outcomes. Among 1370 RSV-positive patients, 49.9% of the patients (n = 683) were hospitalized at or within 3 days of RSV diagnosis with a median length of stay of 6 days (interquartile range [IQR]: 4-9 days), 38.8% were diagnosed with RSV-related respiratory complications (n = 532) and 1.5% died during the hospitalization episode (n = 20). A total of 22.5% of hospitalized patients (n = 154) received critical care during the hospitalization episode. The median cost of each RSV episode was USD539 (IQR: USD167-USD2106) and was higher among hospitalized patients (median: USD2112; IQR: USD1379-USD3182) compared with nonhospitalized patients (median: USD167; IQR: USD112-USD276). RSV infection represents a potentially important contributor to healthcare resource use and medical costs among children <2 years old in Thailand. Coupled with epidemiologic data, findings from our study will be useful to illustrate the overall economic burden associated with RSV infection among children in Thailand.

Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection: A multi-country prospective cohort study in Europe.

Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs+productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs.

Respiratory syncytial virus reinfections among infants and young children in the United States, 2011-2019.

Although respiratory syncytial virus (RSV) immunoprophylaxis is recommended for high-risk infants, the American Academy of Pediatrics (AAP) recommends against immunoprophylaxis in the same season following a breakthrough hospitalization due to limited risk for a second hospitalization. Evidence in support of this recommendation is limited. We estimated population-based re-infection rates from 2011-2019 in children <5 years since RSV risk remains relatively high in this age group. Using claims data from private insurance enrollees, we established cohorts of children <5 years who were followed to ascertain annual (July 1-June 30) and seasonal (November 1- February 28/29) RSV recurrence estimates. Unique RSV episodes included inpatient encounters with RSV diagnosis ≥30 days apart, and outpatient encounters ≥30 days apart from each other as well as from inpatient encounters. The risk of annual and seasonal re-infection was calculated as the proportion of children with a subsequent RSV episode in the same RSV year/season. Over the 8 assessed seasons/years (N = 6,705,979) and across all age groups annual inpatient and outpatient infection rates were 0.14% and 1.29%, respectively. Among children with a first infection, annual inpatient and outpatient re-infection rates were 0.25% (95% confidence interval (CI) = 0.22-0.28) and 3.44% (95% CI = 3.33-3.56), respectively. Both infection and re-infection rates declined with age. While medically-attended re-infections contributed numerically only a fraction of the total RSV infections, re-infections among those with previous infection in the same season were of similar magnitude as the general infection risk, suggesting that a previous infection may not attenuate the risk for a re-infection.

2198. Healthcare Utilization During Acute Medically Attended Respiratory Syncytial Virus (RSV) Episodes among Infants in the United States

Abstract Background Healthcare utilization during acute medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) episodes remains poorly characterized, particularly among term infants without comorbidities. Describing the care incurred during these episodes may provide important information regarding the impact of MA RSV LRTI. Objective: Estimate the occurrence and average number of outpatient, emergency department (ED), and inpatient visits during infants' first RSV season. Methods Using deidentified insurance claims data (MarketScan Commercial ®, MSC; MarketScan Medicaid ®, MSM; Optum Clinformatics ®, OC), we assembled a cohort of infants born in the United States between April 1, 2016 and February 29, 2020 and identified their first MA RSV LRTI episode during their first RSV season. We defined an RSV episode as the 7 days following an index RSV diagnosis (inclusive of the diagnosis date), allowing for two alternative definitions of the index diagnosis—a specific definition, based on ICD-10 codes explicitly indicating RSV, and a sensitive definition, including codes for unspecified bronchiolitis. We calculated the average number of outpatient, ED, and inpatient visits during this episode, stratifying estimates by gestational age and the presence/absence of comorbidities. We also calculated the proportion of episodes involving a given place of service. Results Using the specific (sensitive) definitions, infants averaged 1.11 (1.19), 0.90 (0.89), and 1.56 (1.39) outpatient visits during their first acute RSV episode, in the MSC, MSM, and OC datasets, respectively (Table). They averaged 0.35 (0.23), 0.51 (0.47), and 0.39 (0.23) visits to the ED and 0.28 (0.14), 0.25 (0.14), and 0.23 (0.11) inpatient stays. While MA RSV LRTI episodes among infants who were preterm and/or had other comorbidities (comorbidity groups B and C) were more likely to involve an ED or inpatient visit, up to 21% (10%) of episodes among otherwise healthy term infants involved an inpatient stay. Conclusion Up to 1 in 5 infants experiencing an MA RSV LRTI episode during their first RSV season visited an inpatient setting, including between 9% and 21% of otherwise healthy term infants. This study was funded by Sanofi and AstraZeneca. Disclosures Jason Gantenberg, PhD, MPH, Sanofi: Grant/Research Support Robertus van Aalst, PhD, MSc, Sanofi: Stocks/Bonds David R. Diakun, BS, Sanofi: Employed by IBM Watson Health which was contracted by Sanofi to perfom outcomes research|Sobi: Employed by IBM Watson Health which was contracted by Sobi to conduct the study Christopher B. Nelson, PhD MPH, Sanofi: employee|Sanofi: Stocks/Bonds David A. Savitz, PhD, Sanofi-Pasteur: Grant/Research Support|Sanofi-Pasteur: Honoraria Andrew R. Zullo, PharmD, PhD, Sanofi: Grant/Research Support.

#54 Morbidity and Mortality Associated with Respiratory Syncytial Virus (RSV) Among Pediatric Solid Organ Transplant (SOT) Recipients: Preliminary Results from a Multi-Site U.S. Study.

Abstract Background RSV is the most common lower respiratory tract infection (LRTI) among children. Serious adverse outcomes are more likely among immunocompromised patients, including progression to pneumonia, respiratory failure, and increased mortality rates. We present interim analyses results from a secondary data use multi-site study to characterize the morbidity and mortality associated with RSV infection among pediatric SOT patients. Method Pediatric (&amp;lt; 18 years old at transplant) SOT recipients from 10 U.S. transplant centers from the Pediatric Infectious Diseases Transplant Network (PIDTRAN) who underwent SOT between 2010 and 2019 and were RSV positive within 365 days of SOT were identified from medical records. Demographics, underlying condition, and clinical characteristics were abstracted and entered in an electronic REDCap survey. Descriptive statistics were used to characterize the clinical course and outcomes of RSV infection. Results In total, 40 SOT patients were eligible for analysis with 40 (93%) reporting 1 case of RSV within 365 days of transplant and 3 (7%) reported 2 episodes resulting in 43 RSV episodes. Over half (24, 60%) were male, 24 (60%) were white/Caucasian, with a median age of 2 years at the time of RSV diagnosis. The majority received 1 SOT (80%) prior to RSV diagnosis. The most common transplanted organ was liver 17 (42%) followed by heart 14 (36%) and kidney 9 (22%). Among the 43 episodes reported, almost half (46.5%) were diagnosed with LRTI at the time of RSV diagnosis and 29 (67.4%) required hospitalization. Among the 43 episodes, none received palivizumab and 1 (2.3%) received IVIG in the 4 weeks prior to RSV diagnosis. Nearly half (21, 48.8%) received oxygen support at least 4 hours per day (at least one day) with 3 (15%) requiring ventilator support. Only 2 (5%) were treated with ribavirin while 3 (7%) received IVIG within 28 days for the treatment of RSV. None received palivizumab within 28 days of diagnosis for RSV treatment. Among those who initially presented with upper respiratory tract infection, 2 (10%) progressed to LRTI after initial diagnosis of a URTI. One (2.4%) death related to RSV was reported. Conclusion Preliminary results from this continuing multi-site study demonstrate RSV is an ongoing concern among SOT recipients with approximately half developing LRTI and two thirds requiring hospitalization. These data help our understanding of RSV infections in this population and inform future prospective study designs to better define RSV risk as well as help address optimal prophylaxis and treatment strategies for SOT recipients at risk for severe illness.

#53 Morbidity and Mortality Associated with Respiratory Syncytial Virus (RSV) Among Pediatric Hematopoietic Cell (HCT) Recipients: Preliminary Results from a Multi-Site U.S. Study.

Abstract Background RSV is the most common lower respiratory tract infection (LRTI) among children. Serious adverse outcomes are more likely among immunocompromised patients, including progression to pneumonia, respiratory failure, and increased mortality rates. We present interim analysis results from a multi-site study to characterize morbidity and mortality associated with RSV infection among pediatric HCT patients. Method Pediatric (&amp;lt; 18 years old at transplant) HCT recipients from 10 U.S. transplant centers part of the Pediatric Infectious Diseases Transplant Network (PIDTRAN) who underwent HCT between 2010 and 2019 and were RSV positive during pre-transplant conditioning or within 365 days of HCT were identified from medical records. Demographics, underlying condition, and clinical characteristics were abstracted and entered in an electronic REDCap survey. Descriptive statistics were used to characterize the clinical course and outcomes of RSV infection. Results In total, 108 HCT patients were eligible with 108 (96%) reporting 1 case of RSV within 365 days of transplant and 5 (4%) reported 2 episodes resulting in 113 RSV episodes included in the analysis. Approximately half (53.7%) were male, 53 (49.1%) were white/Caucasian, with a median age of 7 years at the time of RSV diagnosis. The majority only received 1 HCT (84%) prior to RSV diagnosis. The most common HCT was allogeneic type (77.8%), 63 (59%) received myeloablative conditioning, and 23 (22.3%) were t-cell depleted. Just over one third (38%) had received systemic steroids in the 2 weeks prior to RSV diagnosis. Among the 113 episodes, 3 (2.7%) received palivizumab and 34 (30%) received IVIG in the 4 weeks prior to RSV diagnosis. One fourth (25.6%) were hospitalized due to RSV and 13 (11.5%) were diagnosed with LRTI at presentation and 3 (2.7%) progressed to LRTI after initial diagnosis of a URTI. Fifteen (13.3%) received at least 4 hours of oxygen support each day (at least one day), including 2 (13.3%) requiring mechanical ventilation. A quarter (24.8%) were treated with ribavirin, 10 (9%) received IVIG, and 15 (13.4%) received palivizumab for treatment of RSV. Seven (6.3%) deaths related to RSV were reported. Conclusion Preliminary results from this continuing multi-site study demonstrate RSV is an ongoing concern among HCT recipients with 1 in 10 developing LRTI and a quarter requiring hospitalization. These data help our understanding of RSV infections in this population and inform future prospective study designs to better define RSV risk as well as help address optimal prophylaxis and treatment strategies for HCT recipients at risk for severe illness.

Cost of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection Management in Young Children at the Regional and Global Level: A Systematic Review and Meta-Analysis.

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event. Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society.

Estimates for quality of life loss due to Respiratory Syncytial Virus.

BackgroundIn children aged <5 years in whom severe respiratory syncytial virus (RSV) episodes predominantly occur, there are currently no appropriate standardised instruments to estimate quality of life years (QALY) loss.ObjectivesWe estimated the age‐specific QALY loss due to RSV by developing a regression model which predicts the QALY loss without the use of standardised instruments.MethodsWe conducted a surveillance study which targeted confirmed RSV episodes in children aged <5 years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases). All participants were asked to complete questions regarding their health during the infection, with the suspected cases additionally providing health‐related quality of life (HR‐QoL) loss estimates by completing EQ‐5D‐3L‐Y or EQ‐5D‐3L instruments. We used the responses from the suspected cases to calibrate a regression model which estimates the HR‐QoL and QALY loss due to infection.FindingsFor confirmed RSV cases in children under 5 years of age who sought health care, our model predicted a QALY loss per RSV episode of 3.823 × 10−3 (95% CI 0.492‐12.766 × 10−3), compared with 3.024 × 10−3 (95% CI 0.329‐10.098 × 10−3) for under fives who did not seek health care. Quality of life years loss per episode was less for older children and adults, estimated as 1.950 × 10−3 (0.185‐9.578 × 10−3) and 1.543 × 10−3 (0.136‐6.406 × 10−3) for those who seek or do not seek health care, respectively.ConclusionEvaluations of potential RSV vaccination programmes should consider their impact across the whole population, not just young child children.

CHARACTERISTICS AND OUTCOMES AFTER RESPIRATORY SYNCYTIAL VIRUS INFECTION AMONG PATIENTS WITH LUNG TRANSPLANTATION

SESSION TITLE: Outcomes of Respiratory Infections in the Immunocompromised Host SESSION TYPE: Original Investigations PRESENTED ON: 10/20/2019 2:15 PM - 3:15 PM PURPOSE: To describe the characteristics and outcomes in a large cohort of LT patients with respiratory syncytial virus (RSV) infection and elucidate the predictors of one-year survival. METHODS: This was a retrospective chart review study of LT patients with RSV infection between 2013 & 2017 (90 episodes among 87 patients; mean age 56.3±13.1 yrs, M:F 52: 35). Positive respiratory viral multiplex PCR assay confirmed the diagnosis of RSV. Baseline characteristics, presenting features, lung functions pre- and post-RSV episode, management strategies, and one-year survival were reviewed. Variables were compared among patients who survived to one year after RSV versus those who did not. RESULTS: The average time from LT to RSV infection was 34 months. Chronic lung allograft dysfunction (CLAD) was established at the time of RSV among 28 patients. More than three-fourth of the episodes were associated with lower respiratory tract (LRT) symptoms, while a third had radiological or CT changes at presentation. Hospital management (97.8%) was ubiquitous with 31.1% requiring ICU admission. Treatment included inhaled ribavirin (95.6%), palivizumab (95.6%) and pulse steroids (85.6%). The mean length of hospital stay was 8.4±4.7 days and two patients did not survive to discharge. At one year follow up 12 patients had died, with 7 deaths related to progressive CLAD (five of the seven had established CLAD before RSV). The incidence of new diagnosis of CLAD during the year after RSV was 13.8%. On univariate analysis, one year survivors had higher median FVC (2.8vs 1.96L; p=0.006) and FEV1 (2.15 vs 1.44 L; p=0.002) during the 3 months preceding the RSV episode. Established CLAD before the infection (30.4% vs 8.9%, p=0.01), presence of CT changes 44.4% vs 11.1%, p=0.007), and ventilator support (42.9% vs 12%, p=0.026) were associated with increased risk of one-year mortality. After adjusting for age and type of transplant, history of CLAD (adjusted OR: 5.7, 1.42-22.7; p=0.014) and presence of CT infiltrates (11.1, 1.85-67; p=0.009) were associated with one year mortality. CONCLUSIONS: RSV infection occurs frequently after LT. A significant proportion of patients develop parenchymal infiltrates and get acutely ill needing ICU admission. The overall hospital mortality, one year mortality, and the risk of new CLAD after an RSV infection in the current cohort is lower than previously reported. Previous diagnosis of CLAD and presence of CT infiltrates is associated with one-year mortality after RSV infection. CLINICAL IMPLICATIONS: In the largest series to date of RSV infections in a contemporary cohort of LT patients, the early and late outcomes after RSV infection appear to be improving. Aggressive management protocols based upon the early institution of multimodality pharmacotherapy may be associated with favorable outcomes. DISCLOSURES: My spouse/partner as a Employee relationship with St Jude’s Medical Please note: $20001 - $100000 Added 03/15/2019 by Amit Banga, source=Web Response, value=Salary Investigator relationship with Mallinckrodt pharmaceutical Please note: >$100000 Added 03/15/2019 by Amit Banga, source=Web Response, value=Grant/Research Support No relevant relationships by Srinivas Bollineni, source=Web Response No relevant relationships by John Joerns, source=Web Response No relevant relationships by Vaidehi Kaza, source=Web Response No relevant relationships by Ricardo La Hoz, source=Web Response No relevant relationships by Isaac Lill, source=Web Response No relevant relationships by Luke Mahan, source=Web Response No relevant relationships by Manish Mohanka, source=Web Response No relevant relationships by Fernando Torres, source=Web Response No relevant relationships by April Wiggins, source=Web Response

Treatment stratification of respiratory syncytial virus infection in allogeneic stem cell transplantation

Due to paucity of evidence to guide management of allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients with respiratory syncytial virus (RSV) infections national and international guidelines make disparate recommendations. The outcomes of allo-HSCT recipients with RSV infection between 2015 and 2017 were assessed using the following treatment stratification; upper respiratory tract infections (URTI) being actively monitored and lower respiratory tract infections (LRTI) treated with short courses of oral ribavirin combined with intravenous immunoglobulin (IVIG, 2g/kg). During the study period 49 RSV episodes were diagnosed (47% URTI and 53% LRTI). All patients with URTI recovered without pharmacological intervention. Progression from URTI to LRTI occurred in 15%. Treatment with oral ribavirin given until significant symptomatic improvement (median 7 days [3-12]) and IVIG for LRTI was generally well tolerated. RSV-attributable mortality was low (2%). In this cohort study, we demonstrate that active monitoring of allo-HSCT patients with RSV in the absence of LRTI was only associated with progression to LRTI in 15% of our patients and therefore appears to be a safe approach. Short course oral ribavirin in combination with IVIG was effective and well-tolerated for LRTI making it a practical alternative to aerosolised ribavirin. This approach was beneficial in reducing hospitalisation, saving nursing times and by using oral as opposed to nebulised ribavirin.

Age-specific incidence rates and risk factors for respiratory syncytial virus-associated lower respiratory tract illness in cohort children under 5 years old in the Philippines.

BackgroundRespiratory syncytial virus (RSV) is one of the main viral causes of lower respiratory tract illness (LRTI), especially in young children. RSV vaccines, including maternal and infant vaccines, are under development; however, more epidemiological studies are needed to develop effective vaccination strategies.ObjectivesTo estimate detailed age‐specific incidence rates and severity of RSV‐associated LRTI (RSV‐LRTI) using data from a community‐based prospective cohort study in the Philippines.Patients/MethodsCohort children who visited health facilities due to acute respiratory symptoms were identified, and nasopharyngeal swabs were collected to detect RSV. The severity of RSV‐LRTI was assessed using the severity definition proposed by the World Health Organization. Risk factors for developing RSV‐LRTI and contribution of SpO2 measurement were also evaluated.ResultsA total of 395 RSV episodes which occurred in children aged 2‐59 months were categorised as 183 RSV‐LRTI, 72 as severe RSV‐LRTI and 29 as very severe RSV‐LRTI. Children aged 3‐5 months had the highest incidence rate of RSV‐LRTI, at 207.4 per 1000 child‐years (95% CI: 149.0‐279.5). Younger age group, place of living and low educational level of caregivers were associated with developing RSV‐LRTI. Clinical manifestations had low levels of agreement with hypoxaemia as measured by pulse oximeter.ConclusionThe highest burden of RSV was observed in young infants aged 3‐5 months, whereas the burden was also high in those aged 12‐20 months. Future vaccination strategies should consider the protection of older children, especially those aged one year, as well as young infants.

117. Effect of Nasopharyngeal Pneumococcal Carriage on RSV and hMPV Illness Severity in Infants in Nepal

BackgroundPneumococcal pneumonia after a preceding respiratory viral illness is associated with morbidity and mortality in infants. Our study sought to determine how pneumococcal carriage impacted illness severity due to respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in infants 0–6 months in a low resource setting in South Asia without pneumococcal vaccination. Previous studies in this population found an overall 79.4% prevalence of pneumococcal carriage in ages 1–36 months with higher rates of carriage among healthy controls when compared with those with respiratory illness.MethodsInfants were enrolled at the time of birth in a maternal influenza immunization trial conducted in rural Nepal from 2011 to 2014. Weekly household-based active surveillance was performed from birth to 6 months to assess for infant respiratory illness, defined as fever, cough, difficulty breathing, wheeze, or otorrhea. Mid-nasal swabs were collected and tested by PCR for RSV, hMPV, and streptococcus pneumoniae with inclusion of first illness episode in the surveillance period. Disease severity was defined using the World Health Organization Integrated Management of Childhood Illness criteria.ResultsAltogether, 247 (73.5%) of 336 infants with RSV and 154 (83.7%) of 184 infants with hMPV had S. pneumoniae detected. Mean age at RSV illness with concurrent pneumococcal carriage was 97.0 days (91.3–102.6) versus 72.8 days (63.3–82.4) for infants without carriage (P < 0.001). Mean age at hMPV illness with concurrent pneumococcal carriage was 101.3 days (93.9–108.7) versus 77.2 days (56.5–98.0) for infants without carriage (P = 0.01). Frequency of reported lower respiratory tract infection did not differ with or without carriage (RSV: 64.4% vs. 65.2% respectively; P = 0.89, hMPV: 52.6% vs. 50.0% P = 0.79). S. pneumoniae PCR cycle threshold value did not differ by duration or severity of RSV or hMPV illness episode.ConclusionHigh rates of pneumococcal carriage were observed with RSV and hMPV illness episodes in a birth cohort of infants in rural Nepal. The majority of infants with RSV or hMPV illness had pneumococcus detected at the time of first observed illness. However, no increase in RSV or hMPV illness severity or duration was seen with pneumococcal carriage. Disclosures H. Y. Chu, sanofi pasteur: Grant Investigator, Grant recipient. Novavax: Grant Investigator, Grant to co-investigator’s institution.

Pediatricians' attitudes and costs of bronchiolitis in the emergency department: A prospective multicentre study

How pediatricians manage bronchiolitis and the derived total costs (direct and indirect) in the emergency department (ED) have not been fully characterized. The aim of the present study is to calculate those costs in a European country. A prospective and observational study, including 10 EDs of tertiary hospitals throughout Spain and during the bronchiolitis season 2010-2011, was performed. Every ED recruited children on random days of the week (3 days per week; always including one non-working day per every week). Recruitment aimed at a total sample size of 600 children. Direct (diagnostic procedures, time spent in the ED and medication) and indirect costs (work hours lost by parents, babysitting, travels, and meals) were collected. Comparisons between bronchiolitis caused by respiratory syncytial virus (RSV) and non-RSV bronchiolitis, as well as costs across severity categories were performed with the Kruskal-Wallis test. A multiple regression model was built to assess the influence of several of the studied factors on the total costs, including a RSV positive test and episode severity as independent variables; and gender, age, attending nursery school, preterm birth, low birth weight, smoker mother during pregnancy, and current smoker father as covariates. From the 664 recruited children, direct mean costs were €213.2 ± 91.8 and indirect ones were €35.9 ± 55.3; the total costs being €249.2 ± 122.9. Costs were significantly higher in children positive to RSV and rose with increased severity. Those associations were maintained in the multiple regression analysis. Although relatively low at the individual level (€249.2, mean total cost) the costs for just the ED expenses of bronchiolitis in Spain would add up to about €20 million per year.

A High Burden of Respiratory Syncytial Virus Associated Pneumonia in Children Less than Two Years of Age in a South East Asian Refugee Population

BackgroundPneumonia is a major cause of childhood mortality and morbidity approximately 1.6 million deaths and 150 million episodes occur annually in children <5 years. Respiratory syncytial virus (RSV) may be responsible for up to 25% of cases and 12% of deaths making it an important potential vaccine target, although data from South East Asia is scarce.MethodsWe followed a birth cohort of Burmese refugee children, born over a one year period, for two years. Pneumonia episodes were diagnosed using WHO criteria. A chest radiograph, nasopharyngeal aspirate and non-specific markers of infection were taken during each episode.ResultsThe incidence of RSV-associated pneumonia was 0.24 (95% CI 0.22–0.26) episodes per child year. All children with pneumonia received antibiotic treatment, following WHO guidelines. The highest incidence was in the 2–12 month age group. The commonest diagnosis in a child with RSV-associated pneumonia was non-severe pneumonia (239/362∶66.0%), however the incidence of RSV-associated severe or very severe pneumonia was 0.08 (95% CI 0.01–0.10) episodes per child year. Birth in the wet season increased the risk of severe disease in children who had their first episode of RSV-associated pneumonia aged 2–11 months (OR 28.7, 95% CI 6.6–125.0, p<0.001). RSV episodes were highly seasonal being responsible for 80.0% of all the pneumonia episodes occurring each October and November over the study period.ConclusionsThere was a high incidence of RSV associated pneumonia in this refugee population. Interventions to prevent RSV infection have the potential to reduce the incidence of clinically diagnosed pneumonia and hence unnecessary antibiotic usage in this population.

Timing of monoclonal antibody for seasonal RSV prophylaxis in the United Kingdom

Respiratory syncytial virus (RSV) infection produces more severe disease and increased hospitalization rates in high-risk babies. The monoclonal antibody palivizumab offers protection against complications, and the first of five monthly doses should be administered before the onset of community RSV activity. However, the required real-time prediction of this onset is problematic. We attempted to identify seasonal RSV patterns by retrospectively examining 10 years of laboratory reports for RSV and clinical episode reports for certain respiratory presentations in both primary and secondary care. Analysis of hospital laboratory reports, incidence of acute bronchitis in primary care, and hospital admissions for acute bronchitis and bronchiolitis in young children revealed a consistent increase in RSV activity during week 43 each year. Promptly commencing prophylaxis during the second week of each October (week 42) would precede the onset of the RSV season in the United Kingdom, and provide coverage until its decline in mid-March.

Morbidity and health care resource utilization subsequent to respiratory syncytial virus hospitalization among infants born at 33 to 35 completed weeks gestation

Respiratory syncytial virus (RSV) is a major cause of morbidity in infants. Data from a Canadian prospective cohort study on risk factors for RSV hospitalization were used to assess the impact of RSV hospitalizations on subsequent morbidity and mortality in infants born at 33 to 35 weeks gestation. This was a case–control analysis conducted within a cohort of 1857 infants born at 33 to 35 weeks gestation in Canada during two consecutive RSV seasons (2001–2002). There were 96 cases with confirmed ( n = 66) or probable RSV ( n = 30) hospitalization. Controls ( n = 96) were infants in the cohort that did not have RSV and were matched to cases for gestation, small for gestational age, gender, and presence of chronic conditions at discharge after birth, as well as for daycare attendance, maximum number of people in the house, maximum number of smokers, breast feeding, and siblings under 5 years old attending daycare. Follow-up was from the date of discharge after birth to 1 month after the end of the local RSV season (mean: 4.4, range: 1–9 months). Measures of health care utilization and morbidity for the RSV cases were ascertained subsequent to the index RSV hospitalization and for the controls subsequent to discharge after birth. Compared with matched controls, infants with a confirmed RSV-positive hospitalization ( n = 66) had significantly higher rates of emergency room visits (RR = 3.7; P = 0.033) and respiratory tract episodes (RR = 2.15; P < 0.001), and increased risk for rehospitalization after the RSV episode (RR = 12.35; P = 0.093). Infants hospitalized for positive or probable RSV ( n = 96) had significantly higher rates of emergency room visits (RR = 3.52; P = 0.004) and respiratory tract episodes (RR = 2.41; P < 0.001), and increased risk for rehospitalization (RR = 3.51; P = 0.045). RSV hospitalizations in 33- to 35-week-gestation infants are associated with a significant increase in morbidity and health care resource utilization subsequent to and not including those for the RSV infection. Consideration of these outcomes is essential in evaluating benefit of prophylaxis against RSV.