Respiratory Syncytial Virus: Epidemiology, Burden of Disease, and Clinical Update.

Respiratory syncytial virus (RSV) is a common viral pathogen that accounts about 33 million cases of acute lower respiratory tract infection (LRTI) worldwide in children under the age of 5 years each year. High-risk populations, particularly preterm infants, those with underlying chronic lung disease, congenital heart disease, or compromised immune systems, are afflicted most significantly. RSV infection is characterized by significant amount of mucus and submucosal edema in the respiratory tract, leading to congestion and, oftentimes, significant respiratory distress. Antigen- and PCR-based testing are used to diagnose RSV infection.

Clinical and economic burden of respiratory syncytial virus in children aged 0-5 years in Italy.

BACKGROUND: Respiratory syncytial virus (RSV) is among the leading causes of hospitalization due to lower respiratory tract infections (LRTIs) in children younger than 5 years worldwide and the second cause of infant death after malaria. RSV infection occurs in almost all the infants before the second year of life with variable clinical severity, often requiring medical assistance. This analysis investigated patients aged 0-5 years with RSV infection focusing on epidemiology, clinical features, and economic burden of RSV-associated hospitalizations in a setting of Italian real clinical practice. METHODS: An observational retrospective analysis was conducted on administrative databases of healthcare entities covering around 2.6 million residents of whom 120,000 health-assisted infants aged < 5 years. From 2010 to 2018, pediatric patients were included in the presence of hospitalization discharge diagnosis for RSV infections, and RSV-related acute bronchiolitis or pneumonia. Epidemiology, demographics, clinical picture and costs were evaluated in RSV-infected patients, overall and stratified by age ranges (0-1, 1-2, 2-5 years) and compared with an age-matched general population. RESULTS: Overall 1378 RSV-infected children aged 0-5 years were included. Among them, the annual incidence rate of RSV-related hospitalizations was 175-195/100,000 people, with a peak in neonates aged < 1 year (689-806/100,000). While nearly 85% of infected infants were healthy, the remaining 15% presented previous hospitalization for known RSV risk factors, like preterm birth, or congenital heart, lung, and immune diseases. The economic analysis revealed that direct healthcare costs per patient/year were markedly higher in RSV patients than in the general population (3605€ vs 344€). CONCLUSIONS: These findings derived from the real clinical practice in Italy confirmed that RSV has an important epidemiological, clinical, and economic burden among children aged 0-5 years. While the complex management of at-risk infants was confirmed, our data also highlighted the significant impact of RSV infection in infants born at term or otherwise healthy, demonstrating that all infants need protection against RSV disease, reducing then the risk of medium and long-term complications, such as wheezing and asthma.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Hemogram-based decision tree models for discriminating COVID-19 from RSV in infants.

OBJECTIVE: Decision trees are efficient and reliable decision-making algorithms, and medicine has reached its peak of interest in these methods during the current pandemic. Herein, we reported several decision tree algorithms for a rapid discrimination between coronavirus disease (COVID-19) and respiratory syncytial virus (RSV) infection in infants. METHODS: A cross-sectional study was conducted on 77 infants: 33 infants with novel betacoronavirus (SARS-CoV-2) infection and 44 infants with RSV infection. In total, 23 hemogram-based instances were used to construct the decision tree models via 10-fold cross-validation method. RESULTS: The Random forest model showed the highest accuracy (81.8%), while in terms of sensitivity (72.7%), specificity (88.6%), positive predictive value (82.8%), and negative predictive value (81.3%), the optimized forest model was the most superior one. CONCLUSION: Random forest and optimized forest models might have significant clinical applications, helping to speed up decision-making when SARS-CoV-2 and RSV are suspected, prior to molecular genome sequencing and/or antigen testing.

RSV-CLASS -Clinical Assessment Severity Score: An easy-to-use clinical disease severity score for respiratory syncytial virus infection in hospitalized children.

Respiratory syncytial virus (RSV) is the most common cause of acute respiratory tract infection in infants and young children often leading to severe disease requiring hospitalization. However, validated tools for systematic assessment of disease severity are lacking. This study aimed at creating and validating a standardized, simple-to-use disease severity score for RSV infection in children-the RSV-CLASS (Clinical Assessment Severity Score). Therefore, data from over 700 RSV-infected children over six winter seasons (2014-2020) was analyzed using univariate and multiple regression analyses for the prediction of lower respiratory tract infection (LRTI) as a proxy for a severe course of the disease. Testing a broad range of respiratory symptoms, they eventually yielded seven items. Performing stepwise selection, these were reduced to the final four items: cough, tachypnea, rales, and wheezing, each receiving one point in the proposed score named RSV-CLASS. The score was calculated for children in two cohorts A and B, one for development and one for validation, with an area under the curve of 0.90 and 0.87, respectively. With a score value of 3 or 4, 97.8% and 100% of the children, respectively, were admitted with LRTI and classified correctly. The RSV-CLASS is a disease severity score based on a neutral, analytical approach using prospective data from a large study cohort. It will contribute to systematically assessing the disease severity of RSV infection and can be used for evidence-based clinical decision-making as well as for research settings.

NMR-based metabolomics of plasma from dairy calves infected with two primary causal agents of bovine respiratory disease (BRD).

Each year, bovine respiratory disease (BRD) results in significant economic loss in the cattle sector, and novel metabolic profiling for early diagnosis represents a promising tool for developing effective measures for disease management. Here, 1H-nuclear magnetic resonance (1H-NMR) spectra were used to characterize metabolites from blood plasma collected from male dairy calves (n = 10) intentionally infected with two of the main BRD causal agents, bovine respiratory syncytial virus (BRSV) and Mannheimia haemolytica (MH), to generate a well-defined metabolomic profile under controlled conditions. In response to infection, 46 metabolites (BRSV = 32, MH = 33) changed in concentration compared to the uninfected state. Fuel substrates and products exhibited a particularly strong effect, reflecting imbalances that occur during the immune response. Furthermore, 1H-NMR spectra from samples from the uninfected and infected stages were discriminated with an accuracy, sensitivity, and specificity ≥ 95% using chemometrics to model the changes associated with disease, suggesting that metabolic profiles can be used for further development, understanding, and validation of novel diagnostic tools.

Performance Assessment of a Rapid Molecular Respiratory Syncytial Virus Point-of-Care Test: A Prospective Community Study in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) causes a substantial burden in older adults. Viral load in RSV-infected adults is generally lower compared to young children, which could result in suboptimal sensitivity of RSV diagnostics. Although the Xpert® Xpress Flu/RSV assay has been used in routine clinical care, its sensitivity to diagnose RSV infection in older adults is largely unknown. We aimed to compare the performance of the Xpert® Xpress Flu/RSV assay with real-time reverse-transcription polymerase chain reaction (RT-PCR) in home-dwelling older adults (≥60 years of age). METHODS: Nasopharyngeal swabs were tested with Xpert® Xpress Flu/RSV and compared to RSV RT-PCR in older adults with acute respiratory tract infections with different levels of disease severity. RESULTS: We studied 758 respiratory samples from 561 older adults from 2 consecutive RSV seasons. Thirty-five (4.6%) samples tested positive for RSV by at least 1 of the assays, of which 2 samples were negative by Xpert® Xpress Flu/RSV and 3 samples by real-time RT-PCR. The positive percentage agreement (PPA) was 90.9% (95% confidence interval [CI], 76.4%-96.8%) and negative percentage agreement was 99.7% (95% CI, 99.0%-99.9%). Viral loads were low (≤103 copies/mL or cycle threshold value ≥34) in all cases with discordant results for the 2 assays. CONCLUSIONS: The PPA of Xpert® Xpress Flu/RSV compared to routine RT-PCR is high for RSV detection in home-dwelling older adults. The assay is fast and easy to use at the point of care. CLINICAL TRIALS REGISTRATION: NCT03621930.

Comparison of Clinical, Demographic Features, and Costs in Respiratory Syncytial Virus, Rhinovirus, and Viral Co-infections in Children Hospitalized with Viral Infections of the Lower Respiratory Tract.

Viruses are the most common cause of lower respiratory tract infections (LRTIs) in children. Our study aimed to shed light on co-infection by comparing it with the most common single agents, such as respiratory syncytial virus (RSV) and rhinovirus (RV), in terms of epidemiological, clinical, laboratory findings, and cost. This retrospective study analyzed medical records pertaining to infants aged below 5 years, hospitalized with a diagnosis of LRTI with RSV, RV, or co-infection. The study group consisted of 199 children, RSV was detected in 116 patients (58.3%), RV in 46 (23.1%), and co-infections in 37 (18.6%). The average age of patients infected with RV was higher (P = 0.006), and the length of hospital stay of patients infected with RSV was longer (P = 0.03) than that with other agents. There was no significant difference between the groups in terms of oxygen requirement, intensive care unit admission, intubation, and development of complications. The cost was significantly higher in the RSV group (P = 0.02) compared to the other groups. Viral co-infections, RSV, and RV constitute an important part of the etiology in patients aged below 5 years; co-infections do not cause more severe clinical findings compared to single viral agents.

Comparative assessment of reported symptoms of influenza, respiratory syncytial virus, and human metapneumovirus infection during hospitalization and post-discharge assessed by Respiratory Intensity and Impact Questionnaire.

BACKGROUND: The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™, to assess and compare the burden of respiratory infection symptoms for patients with influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) infection, with or without core risk factors (CRF) (age ≥65; chronic heart, renal, obstructive pulmonary disease; asthma). METHODS: This was a prospective cohort study in adult patients hospitalized with acute respiratory tract infection (40 centers, 12 countries) during two consecutive influenza/RSV/hMPV seasons (2017-2019). The RiiQ™ Symptom Scale and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) were assessed by interview at two timepoints during hospitalization and at 1, 2, and 3 months post-discharge. RESULTS: Mean lower respiratory tract (LRT) symptom scores were higher for RSV and hMPV participants compared to influenza at 48 h after enrollment/early discharge (p = 0.001) and 3 months post-discharge (p = 0.007). This was driven by LRT symptoms, including shortness of breath (SOB) (p < 0.01) and wheezing (p < 0.01) during hospitalization, and SOB (p < 0.05) and cough (p < 0.05) post-discharge. Participants with CRF reported more moderate-to-severe SOB (p < 0.05) and wheezing (p < 0.05) compared to CRF(-) participants post-discharge. EQ-5D-5L scores were moderately associated with RiiQ™ LRT and systemic symptoms domains. CONCLUSIONS: Results from the HARTI study suggest that in the study population, LRT symptoms were more severe for RSV and hMPV groups and for patients with CRF. RiiQ™ Symptom Scale scores shows a moderate association with EQ-5D-5L indicating that the RiiQ™ may provide useful insights and offer advantages over other measures for use in interventional RSV adult clinical studies.

Evaluation of a standardised protocol to measure the disease burden of respiratory syncytial virus infection in young children in primary care.

BACKGROUND: A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years. METHODS: The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2-4 years) and PedsQL™4.0 infant scales (0-2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions. RESULTS: Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children. CONCLUSION: RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9-year retrospective multicentre study.

OBJECTIVES: To analyse functional outcome parameters according to antimicrobial treatments after respiratory syncytial virus (RSV)-confirmed infection in adult lung transplant recipients. METHODS: A 9-year retrospective multicentre cohort study (2011-19) included adult lung transplant recipients with RSV-confirmed infection. The first endpoint determined new allograft dysfunction (acute graft rejection and chronic lung allograft dysfunction (CLAD)) 3 months after infection. Then baseline and 3 months' postinfection forced expiratory volume in 1 second (FEV1) values were compared according to antimicrobial treatment. Univariate logistic regression analysis was performed. RESULTS: RSV infection was confirmed in 77 of 424 lung transplant recipients (estimated incidence of 0.025 per patient per year; 95% confidence interval 0.018-0.036). At 3 months, 22 recipients (28.8%) developed allograft dysfunction: ten (13%) possible CLAD, six (7.9%) acute rejection and six (7.9%) CLAD. Recipients with the lowest preinfection FEV1 had a greater risk of developing pneumonia (median (interquartile range) 1.5 (1.1-1.9) vs. 2.2 (1.5-2.4) L/s, p 0.003) and a higher odds of receiving antibiotics (1.6 (1.3-2.3) vs. 2.3 (1.9-2.5) L/s, p 0.017; odds ratio 0.52, 95% confidence interval 0.27-0.99). Compared to tracheobronchitis/bronchiolitis, RSV-induced pneumonia led more frequently to hospitalization (91.7%, 22 vs. 58.0%, 29, p 0.003) and intensive care unit admission (33.3%, 8 vs. 0, p < 10-3). For ribavirin-treated recipients (24.7%, 19) and azithromycin prophylaxis (50.6%, 39), 3-month FEV1 values were not different from untreated recipients. The overall mortality was 2.5% at 1 month and 5.3% at 6 months, unrelated to RSV. CONCLUSIONS: At 3 months after RSV-confirmed infection, 22 recipients (28.8%) had new allograft dysfunction. Ribavirin treatment and azithromycin prophylaxis did not prevent FEV1 decline.

Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17.

BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

Respiratory syncytial virus hospitalisations among young children: a data linkage study.

We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8-6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Maori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.

Pediatric intensive care unit admission due to respiratory syncytial virus: Retrospective multicenter study.

BACKGROUND: We investigated the characteristics and clinical outcomes of respiratory syncytial virus (RSV)-related pediatric intensive care unit (PICU) hospitalization and assessed the palivizumab (PZ) prophylaxis eligibility according to different guidelines from Korea, EU, and USA. METHODS: In this multicenter study, children <18 years of age hospitalized in six PICU from different hospitals due to severe RSV infection between September 2008 and March 2013 were included. A retrospective chart review was performed. RESULTS: A total of 92 patients were identified. The median length of PICU stay was 6 days (range, 1-154 days) and median PICU care cost was USD2,741 (range, USD556-98 243). Of 62 patients who were <2 years old at the beginning of the RSV season, 33 (53.2%) were high-risk patients for severe RSV infection. Hemodynamically significant congenital heart disease (22.6%) was the most common risk factor, followed by chronic lung disease (11.3%), neuromuscular disease or congenital abnormality of the airway (NMD/CAA) (11.3%), and prematurity (8.1%). The percentage of patients eligible for PZ prophylaxis ranged from 38.7% to 48.4% based on the guidelines, but only two (2.2%) received PZ ≤30 days prior to PICU admission. The median duration of mechanical ventilation was longer in children with NDM/CAA than in those without risk factors (26 days; range, 24-139 days vs 6 days, range, 2-68 days, P = 0.033). RSV-attributable mortality was 5.4%. CONCLUSIONS: Children <2 years old with already well-known high risks represent a significant proportion of RSV-related PICU admissions. Increasing of the compliance for PZ prophylaxis practice among physicians is needed. Further studies are needed to investigate the burden of RSV infection in patients hospitalized in PICU, including children with NMD/CAA.

Impact of molecular point-of-care testing on clinical management and in-hospital costs of patients suspected of influenza or RSV infection: a modeling study.

BACKGROUND: At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point-of-care (POC) diagnostics on patient management and in-hospital costs. METHOD: Prospective collection of data on resource utilization within the hospital from consecutive patients 18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (on the basis of routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from the hospital, too (scenario 2). RESULTS: A total of 283 patients were included, of whom 217 (76.7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. Fifty-four percent of patients tested negative, of which 79% were kept in isolated care waiting for test results, with a median duration of 24 hours. Median length of stay was 6.0 days. Mean total in-hospital costs per patient were € 5243. Introducing POC would lower mean costs per patient to € 4904 (scenario 1) and € 4206 (scenario 2). At the hospital level, this would result in a total cost reduction of € 95 937 to € 293 471 in a single influenza season. CONCLUSIONS: Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time-to-diagnosis, hospital stay and, thereby, in-hospital costs.

Burden of hospital admissions caused by respiratory syncytial virus (RSV) in infants in England: A data linkage modelling study.

OBJECTIVES: Current national estimates of respiratory syncytial virus (RSV)-associated hospital admissions are insufficiently detailed to determine optimal vaccination strategies for RSV. We employ novel methodology to estimate the burden of RSV-associated hospital admissions in infants in England, with detailed stratification by patient and clinical characteristics. METHODS: We used linked, routinely collected laboratory and hospital data to identify laboratory-confirmed RSV-positive and RSV-negative respiratory hospital admissions in infants in England, then generate a predictive logistic regression model for RSV-associated admissions. We applied this model to all respiratory hospital admissions in infants in England, to estimate the national burden of RSV-associated admissions by calendar week, age in weeks and months, clinical risk group and birth month. RESULTS: We estimated an annual average of 20,359 (95% CI 19,236-22,028) RSV-associated admissions in infants in England from mid-2010 to mid-2012. These admissions accounted for 57,907 (95% CI 55,391-61,637) annual bed days. 55% of RSV-associated bed days and 45% of RSV-associated admissions were in infants <3 months old. RSV-associated admissions peaked in infants aged 6 weeks, and those born September to November. CONCLUSIONS: We employed novel methodology using linked datasets to produce detailed estimates of RSV-associated admissions in infants. Our results provide essential baseline epidemiological data to inform future vaccine policy.

Respiratory health inequality starts early: The impact of social determinants on the aetiology and severity of bronchiolitis in infancy.

AIM: To define the impact of demographics on the incidence, aetiology and clinical course of viral bronchiolitis in infants younger than 2 years of age. METHODS: Retrospective case review of all viral bronchiolitis admissions for patients aged younger than 2 years old from January 1 2014 to 31 December 2015 at Wellington Regional Hospital, New Zealand. Demographic data, second-hand smoke exposure (SHSE) and presence of predisposing conditions were collected, along with outcome data including use of respiratory support and intensive care unit (ICU) admission. This was compared to background rates calculated from regional census data. RESULTS: There were 556 admissions included (11% of paediatric medical admissions); 49% tested positive for respiratory syncytial virus (RSV) (84% tested), and 40% of admissions received positive pressure respiratory support and 10% ICU admission. Admission rates ranged from 9.6 to 77 per 1000/year, with higher rates seen in those from areas of high deprivation. Admission rates by deprivation varied according to aetiology. RSV-positive admission rates increased from 9.7 per 1000/year to 24.6 per 1000/year in the least to most deprived areas, whereas non-RSV admissions showed even greater disparity, increasing from 10.1 per 1000/year to 37.5 per 1000/year (both P < 0.0001). CONCLUSIONS: This study further reinforces that material deprivation contributes significantly to poor health outcomes that are apparent in infancy. SHSE is a potent risk factor for adverse respiratory outcomes in this patient population. Ongoing efforts to eradicate smoking and reduce material inequality need to continue.

Assessment and Validation of Syndromic Case Definitions for Respiratory Syncytial Virus Testing in a Low Resource Population.

Standardized case definitions are needed in decision-making regarding respiratory syncytial virus control strategies, including vaccine evaluation. A syndromic case definition comprising of "wheeze or apnea or cyanosis" could be useful for community-based surveillance of moderate respiratory syncytial virus infection among young infants particularly in resource-limited settings. However, this definition showed modest specificity (29.2%-49.6%), indicating that community-based surveillance may need augmentation with other data.

Incidence and seasonality of respiratory syncytial virus hospitalisations in young children in Denmark, 2010 to 2015.

For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual RSV-associated admissions in children < 5 years-old for the period of 2010-2015. We identified ca 2,500 RSV-associated hospitalisations annually amounting to total direct medical-costs of ca EUR 4.1 million per year. The incidence of RSV-associated hospitalisations peaked in infants 1-2 months of age followed by infants 2-3 months of age, and infants < 1 month of age, respectively. Infant boys were at higher risk of severe RSV infection as compared to infant girls: male-to-female ratio peaked with 1.4 at four months of age and gradually levelled out with increasing age to 1.0 at 4 years of age. Five RSV-associated deaths were identified. Our findings demonstrate that in a western country as Denmark, RSV constitutes a considerable burden on childhood health. Furthermore, the best approach to reduce the high incidence of RSV-associated hospitalisations in young infants < 3 months of age may be maternal vaccination due to general challenges in achieving sufficient and protective immune responses in young infants.