Respiratory Syncytial Virus Prevention Strategies Research Articles

A Model-Based Estimation of RSV-Attributable Incidence of Hospitalizations and Deaths in Italy Between 2015 and 2019.

Respiratory syncytial virus (RSV) incidence is known to be underestimated in adults due to its infrequent diagnostic testing and lower sensitivity of single nasal/nasopharyngeal swab PCR testing outside of the early childhood period. RSV can trigger acute cardiac events as well as cause respiratory disease. Consequently, we used a model-based study to estimate RSV-attributable hospitalization and mortality incidence among adults in Italy between 2015 and 2019. Through a database predisposed by CREA Sanità, by extracting monthly data from the Italian hospitalization collection data of the Ministry of Health and the Italian National Institute of Statistics (ISTAT) data (mortality), we estimated yearly RSV-attributable incidence of events for different cardiorespiratory outcomes. We used a quasi-Poisson regression model, which accounted for periodic and aperiodic time trends and viral activity proxies. The yearly RSV-attributable cardiorespiratory hospitalization incidence increased with age and was highest among adults aged≥75 years (1064-1527 cases per 100,000 person-years). Similarly, the RSV-attributable cardiorespiratory mortality rate was highest among persons aged≥75 years (59-85 deaths per 100,000 person-years). Incidence rates for RSV-attributable hospitalizations and RSV-attributable mortality were on average 2-3 times higher for cardiorespiratory than respiratory disease alone. Incidence rate based on RSV-specific ICD codes only were 405-1729 times lower than modeled estimates accounting for untested events. RSV causes a substantial disease burden among adults in Italy and contributes to both respiratory and cardiovascular conditions. Our results emphasize the need for effective RSV prevention strategies, particularly among older adults.

Respiratory Syncytial Virus Hospital Admission Rates and Patients' Characteristics Before the Age of 2 Years in England, 2015-2019.

A granular understanding of respiratory syncytial virus (RSV) burden in England is needed to prepare for new RSV prevention strategies. We estimated the rates of RSV hospital admissions before the age of 2 years in England and described baseline characteristics. A birth cohort of all infants born between March 1, 2015, and February 28, 2017 (n = 449,591) was established using Clinical Practice Research Datalink-Hospital Episode Statistics. Case cohorts included infants with admission for (1) RSV, (2) bronchiolitis, (3) any respiratory tract infection (RTI) <24 months and (4) RSV predicted by an algorithm <12 months. Baseline characteristics were described in the case and comparative cohorts (infants without corresponding admission). Cumulative incidence and admission rates were calculated. Multiple linear regression was used to estimate the proportion of RTI healthcare visits attributable to RSV. The RSV-coded/RSV-predicted case cohorts were composed of 4813/12,694 infants (cumulative incidence: 1.1%/2.8%). Case cohort infants were more likely to have low birth weight, comorbidities and to be born during RSV season than comparative cohort infants, yet >77% were term-healthy infants and >54% were born before the RSV season. During the first year of life, 11.6 RSV-coded and 34.4 RSV-predicted hospitalizations occurred per 1000 person-years. Overall, >25% of unspecified lower RTI admissions were estimated to be due to RSV. In England, 1 in 91 infants had an RSV-coded admission, likely underestimated by ~3-fold. Most infants were term-healthy infants born before the RSV season. To decrease the total burden of RSV at the population level, immunization programs need to protect all infants.

Parental awareness and attitudes towards prevention of respiratory syncytial virus in infants and young children in Australia.

To assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies. A cross-sectional online survey was implemented targeting "future" and "current" parents of children aged ≤5 years in Australia. From 1992 eligible participants, two non-mutually exclusive subgroups were formed: "current" parents (N = 1931) and "pregnant/planning" parents (N = 464: 403 also "current" parents and 61 "future" parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated with RSV. In multivariable logistic regression analyses, Australian-born parents (aOR = 2.47 [95% CI: 1.48-4.12]), living in the eastern states (e.g., New South Wales: aOR = 6.15 [95% CI:2.10-18.04]), with a university-level education (aOR = 2.61 [95% CI:1.38-4.94]) and being a current parent (aOR = 12.26 [95% CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%). While RSV awareness and immunisation acceptance were high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.

Respiratory Syncytial Virus Infection Among Hospitalized Infants in Four Middle-Income Countries.

Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015-2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth). Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4-6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6-6.5 for 0-2 compared to 9-11-months; P < .01), low weight-for-age z-score (aOR 1.9, 95% CI: 1.2-2.8; P < .01), ICU care after birth (aOR 1.6, 95% CI: 1.0-2.5; P = .048), and cesarean delivery (aOR 1.4, 95% CI: 1.0-1.8; P = .03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8-1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries.

Bronchiolitis, Regardless of Its Etiology and Severity, Is Associated With Increased Risk of Asthma: A Population-Based Study.

An association exists between severe respiratory syncytial virus (RSV)-bronchiolitis and a subsequent increased risk of recurrent wheezing (RW) and asthma. However, a causal relationship remains unproven. Using a retrospective population-based cohort study (339 814 children), bronchiolitis during the first 2 years of life (regardless of etiology and severity) was associated with at least a 3-fold increased risk of RW/asthma at 2-4 years and an increased prevalence of asthma at ≥5 years of age. The risk was similar in children with mild bronchiolitis as in those with hospitalized RSV-bronchiolitis and was higher in children with hospitalized non-RSV-bronchiolitis. The rate of RW/asthma was higher when bronchiolitis occurred after the first 6 months of life. Our results seem to support the hypothesis of a shared predisposition to bronchiolitis (irrespective of etiology) and RW/asthma. However, 60% of hospitalized bronchiolitis cases in our setting are due to RSV, which should be paramount in decision-making on imminent RSV prevention strategies.

Respiratory Syncytial Virus Disease Burden in Community-Dwelling and Long-Term Care Facility Older Adults in Europe and the United States: A Prospective Study.

Data on respiratory syncytial virus (RSV) disease burden in adults remain scarce. We assessed the burden of confirmed RSV-acute respiratory infections (cRSV-ARIs) in community-dwelling (CD) adults and those in long-term care facilities (LTCFs). In this prospective cohort study covering 2 RSV seasons (October 2019-March 2020 and October 2020-June 2021), RSV-ARIs were identified through active surveillance, in medically stable CD-adults ≥50 years (Europe) or adults ≥65 years in LTCFs (Europe and the United States). RSV infection was confirmed by polymerase chain reaction from combined nasal and throat swabs. Of 1981 adults enrolled, 1251 adults in CD and 664 LTCFs (season 1) and 1223 adults in CD and 494 LTCFs (season 2) were included in the analyses. During season 1, overall incidence rates ([IRs] cases/1000 person-years) and attack rates (ARs) for cRSV-ARIs were 37.25 (95% confidence interval [CI], 22.62-61.35) and 1.84% in adults in CD and 47.85 (CI, 22.58-101.4) and 2.26% in adults in LTCFs. Complications occurred for 17.4% (CD) and 13.3% (LTCFs) of cRSV-ARIs. One cRSV-ARI occurred in season 2 (IR = 2.91 [CI, 0.40-20.97]; AR = 0.20%), without complications. No cRSV-ARIs led to hospitalization or death. Viral pathogens were codetected in ≤17.4% of cRSV-ARIs. RSV is an important cause of disease burden in adults in CD and LTCFs. Despite the observed low severity of cRSV-ARI, our results support the need for RSV prevention strategies among adults ≥50 years old.

Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease, especially in young children. Despite its global impact on healthcare, related to its high prevalence and its association with significant morbidity, the current therapy is still mostly supportive. Moreover, while more than 50 years have passed since the first trial of an RSV vaccine (which unfortunately caused enhanced RSV disease), no vaccine has been approved for RSV prevention. In the last two decades, our understanding of the pathogenesis and immunopathology of RSV have continued to evolve, leading to significant advancements in RSV prevention strategies. These include both the development of new potential vaccines and the successful implementation of passive immunization, which, together, will provide coverage from infancy to old age. In this review, we provide an update of the current treatment options for acute disease (RSV-specific and -non-specific) and different therapeutic approaches focusing on RSV prevention.

Preventing Respiratory Syncytial Virus in Children in France: A Narrative Review of the Importance of a Reinforced Partnership Between Parents, Healthcare Professionals, and Public Health Authorities.

The highly contagious respiratory syncytial virus (RSV) is responsible for up to approximately 50,000 hospitalisations during each RSV season in children aged under 5years in France, with the burden greatest in infants younger than 1year who were born at term. There is a need for a strategy to universally protect young children from RSV infection, and thereby reduce the pressure that RSV places every year on RSV-infected children, their parents, and French healthcare systems. Potential strategies currently undergoing clinical investigation include passive immunisation via maternal vaccination or administration of long-acting monoclonal antibodies at or soon after birth, followed by vaccination later in infancy or childhood. An ongoing partnership and collaboration between parents, public health authorities, and frontline primary healthcare will need to be reinforced once these new RSV prevention strategies are available, to facilitate their use and ensure that all children receive adequate protection from the start of their first RSV season.

Predicted effectiveness of vaccines and extended half-life monoclonal antibodies against RSV hospitalizations in children

Several vaccines and extended half-life monoclonal antibodies (mAbs) against respiratory syncytial virus (RSV) have shown promise in clinical trials. We used age-structured transmission models to predict the possible impact of various RSV prevention strategies including maternal immunization, live-attenuated vaccines, and long-lasting mAbs. Our results suggest that maternal immunization and long-lasting mAbs are likely to be highly effective in preventing RSV hospitalizations in infants under 6 months of age, averting more than half of RSV hospitalizations in neonates. Live-attenuated vaccines could reduce RSV hospitalizations in vaccinated age groups and are also predicted to have a modest effect in unvaccinated age groups because of disruptions to transmission. Compared to year-round vaccination, a seasonal vaccination program at the country level provides at most a minor advantage regarding efficiency. Our findings highlight the substantial public health impact that upcoming RSV prevention strategies may provide.

Epidemiology of respiratory syncytial virus in Japan: A nationwide claims database analysis.

BackgroundRespiratory syncytial virus (RSV) is a major cause of hospitalization for bronchiolitis and pneumonia in infancy. In Japan, limited data are publicly available on RSV epidemiology and clinical characteristics among infants.MethodsThis retrospective study described RSV incidence, seasonality, patient characteristics, resource use, and clinical outcomes among Japanese children <2 years from January 2017 through December 2018. The RSV cases were identified using the Japanese Medical Data Center database.ResultsIn the database, 9,711 and 8,509 RSV patients <2 years were identified in 2017 and 2018, respectively. Of these, 25% required hospitalization. Ninety percent of hospitalized patients did not have a known RSV risk factor. Nineteen percent of hospitalized patients experienced dehydration, and 12% had acute respiratory failure. Hospitalization lasted 1 week on average and 7% required some type of mechanical ventilation. The peak of hospitalizations occurred at 2 months. The incidence of RSV hospitalization in children <2 years was 23.2 per 1,000 person‐years, which increased to 35.4 per 1,000 for infants <6 months. This age group accounted for 40% of all RSV‐associated hospitalizations among children <2 years.ConclusionsRoughly one‐fourth of all RSV patients <2 years were hospitalized. Ninety percent of these did not have an underlying risk condition. This underscores that RSV can cause serious disease among all young children. Three to four out of every 100 Japanese children <6 months were hospitalized for RSV, and this age group accounted for ~40% of all RSV‐associated hospitalizations. Novel and broad‐based RSV prevention strategies, especially those targeting young infants, are needed.

Family and Child Risk Factors for Early-Life RSV Illness

Most infants hospitalized with respiratory syncytial virus (RSV) do not meet common "high-risk" criteria and are otherwise healthy. The objective of this study was to quantify the risks and relative importance of socioeconomic factors for severe, early-life RSV-related illness. We hypothesized several of these factors, particularly those indicating severe social vulnerability, would have statistically significant associations with increased RSV hospitalization rates and may offer impactful targets for population-based RSV prevention strategies, such as prophylaxis programs. We used linked health, laboratory, and sociodemographic administrative data for all children born in Ontario (2012-2018) to identify all RSV-related hospitalizations occurring before the third birthday or end of follow-up (March 31, 2019). We estimated rate ratios and population attributable fractions using a fully adjusted model. A total of 11 782 RSV-related hospitalizations were identified among 789 484 children. Multiple socioeconomic factors were independently associated with increased RSV-related admissions, including young maternal age, maternal criminal involvement, and maternal history of serious mental health and/or addiction concerns. For example, an estimated 4.1% (95% confidence interval: 2.2 to 5.9) of RSV-related admissions could be prevented by eliminating the increased admissions risks among children whose mothers used welfare-based drug insurance. Notably, 41.6% (95% confidence interval: 39.6 to 43.5) of admissions may be prevented by targeting older siblings (eg, through vaccination). Many social factors were independently associated with early-life RSV-related hospitalization. Existing RSV prophylaxis and emerging vaccination programs should consider the importance of both clinical and social risk factors when determining eligibility and promoting compliance.

1719. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis

BackgroundUnderstanding the true magnitude of infant respiratory syncytial virus (RSV) burden is critical for determining the potential public-health benefit of RSV prevention strategies. Although global reviews of infant RSV burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.MethodsWe performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants. We also examined the impact of key study characteristics on these estimates.ResultsAfter review of 3058 articles through January 2020, we identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants < 1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate= 19.4 (95%CI= 17.9–20.9). Study type was associated with RSV hospitalization rates (P =.003), with active surveillance studies having pooled rates per 1000 (11.1; 95%CI: 9.8–12.3) that were half that of studies based on administrative claims (21.4; 95%CI: 19.5–23.3) or modeling approaches (23.2; 95%CI: 20.2–26.2).ConclusionApplying the pooled rates identified in our review to the 2020 US birth cohort suggests that 73,680 to 86,020 RSV-associated infant hospitalizations occur each year. To date, public-health officials have used conservative estimates from active surveillance as the basis for defining US infant RSV burden. The full range of RSV-associated hospitalization rates identified in our review better characterizes the true RSV burden in infants and can better inform future evaluations of RSV prevention strategies.Disclosures John M. McLaughlin, PhD, Pfizer (Employee, Shareholder) Farid L. Khan, MPH, Pfizer (Employee, Shareholder) Heinz-Josef Schmitt, MD, Pfizer (Employee, Shareholder) Yasmeen Agosti, MD, Pfizer (Employee, Shareholder) Luis Jodar, PhD, Pfizer (Employee, Shareholder) Eric Simões, MD, Pfizer (Consultant, Research Grant or Support) David L. Swerdlow, MD, Pfizer (Employee, Shareholder)

Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis.

BackgroundAlthough global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.MethodsWe performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates.ResultsWe reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9–20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8–12.2) that were half that of studies based on administrative claims (21.4; 19.5–23.3) or modeling approaches (23.2; 20.2–26.2).ConclusionsApplying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680–86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.

Incidence of respiratory syncytial virus related health care utilization in the United States.

BackgroundRespiratory Syncytial Virus (RSV) is one of the most frequent causes of acute respiratory infection worldwide. Understanding age-specific health care utilization is necessary to guide effective prevention strategies. This retrospective database analysis assessed the incidence rates of RSV-related health care utilization in the USA over a 7-year period.MethodsEpisodes of RSV were identified in the Truven Health MarketScan® Commercial Claims and Encounters database between 2008 and 2014 using ICD-9-CM codes for pneumonia, bronchiolitis and RSV (480-486, 487.0, 466.1, 491.2, 079.6). Annual RSV-related health care utilization was calculated for the total population, by age group (<1, 1, 2-4, 5-17, 18-49, 50-64, 65-74, 75-84 and ≥85 years) and the proportion of cases for each setting (hospitalization, outpatient, or emergency department [ED] / urgent care [UC]).ResultsOver the 7-year study period, the mean rate of all RSV-associated health care utilization was 2.4 per 1000 person-years, with mean rates ranging from 2.0 to 2.6). The highest rate was seen in infants aged <1 year (mean 79.0 per 1000 over the 7-year period), which decreased with increasing age in the range 2-49 years before increasing with age in older adults (mean rate 8.1 per 1000 over the 7-year period in those ≥85 years). Of all RSV cases, 82% were reported in an outpatient setting, 11% in the ED/UC and 7% were hospitalized.ConclusionsThe annual RSV-related healthcare utilization rates were substantial, especially in infants and young children. These results underscore the need to accelerate the development of RSV prevention strategies to reduce the healthcare burden of RSV.

Respiratory Syncytial Virus-Associated Hospitalizations Among Adults With Chronic Medical Conditions.

In contrast with respiratory disease caused by influenza, information on the risk of respiratory syncytial virus (RSV) disease among adults with chronic medical conditions (CMCs) is limited. We linked population-based surveillance of acute respiratory illness hospitalizations to national administrative data to estimate seasonal RSV hospitalization rates among adults aged 18-80 years with the following preexisting CMCs: chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), diabetes mellitus (DM), and end-stage renal disease (ESRD). Age- and ethnicity-adjusted rates stratified by age group were estimated. Among 883 999 adult residents aged 18-80 years, 281 RSV-positive hospitalizations were detected during 2012-2015 winter seasons. Across all ages, RSV hospitalization rates were significantly higher among adults with COPD, asthma, CHF, and CAD compared with those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50-64 years and adults with DM aged 18-49 years and 65-80 years compared with adults in each age group without these conditions. No increased risk was seen for adults with CVA. The CMC with the highest risk of RSV hospitalization was CHF (incidence rate ratio [IRR] range, 4.6-36.5 across age strata) and COPD (IRR range, 9.6-9.7). Among RSV-positive adults, CHF and COPD were independently associated with increased length of hospital stay. Adults with specific CMCs are at increased risk of RSV hospitalizations. Age affects this relationship for some CMCs. Such populations maybe relevant for future RSV prevention strategies.

Development of a palivizumab specialty pharmacy management program

Background: Palivizumab is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in high risk pediatric patients. Due to the high cost, handling requirements, administration route, and importance of adherence, palivizumab is best managed by specialty pharmacies able to provide robust clinical services. In collaboration with the health system and surrounding pediatric clinics, a specialty pharmacy management program was established to serve patients receiving palivizumab. Aims: To develop a relationship with local pediatric clinics to provide specialty pharmacy services for patients receiving palivizumab. Methods: The patient medication liaison (PML) completed a query of the internal electronic medical record based on diagnosis code to target high risk infants and newborns meeting approval criteria for palivizumab. Providers were notified and palivizumab was prescribed if warranted. During RSV season, internal referrals were also received from the transition of care team directly from the neonatal intensive care unit. An intake form was created for outside clinic/institutions referring pediatrics meeting criteria. The form included: patient, insurance, prescriber, clinical, and prescription information. The PML initiated contact with the parent/guardian and proceeded with benefits investigation. The PML coordinated refills, clinic visits, and nurse visits. The clinical pharmacist provided education on dosing, administration, side-effects, warnings/precautions, importance of adherence, goals of therapy, and RSV prevention strategies. The outcomes of the project include: number of approved prior authorizations, number of prescription fills for Mizzou Specialty Pharmacy, and the number of patients enrolled in patient assistance. Results: From October 2016 through April 2019, the specialty pharmacy worked with two local pediatric clinics. Two hundred and thirty-nine patients were referred to the pharmacy for benefits investigation; 172 prior authorizations (PAs) were approved: 34 triaged to an outside specialty pharmacy, 129 managed by Mizzou Specialty Pharmacy, 18 chose not to pursue. Finally, 48 PAs were denied and 19 patients were approved for patient assistance. Conclusions: Mizzou Specialty Pharmacy successfully developed relationships with local pediatric clinics to serve their patients receiving palivizumab.

Respiratory Syncytial Virus Hospitalization During Pregnancy in 4 High-income Countries, 2010-2016.

Few studies have addressed respiratory syncytial virus (RSV) infection during pregnancy. Among 846 pregnant women hospitalized with respiratory illness and tested for RSV, 21 (2%) were RSV positive, of whom 8 (38%) were diagnosed with pneumonia. Despite study limitations, these data can help inform decisions about RSV prevention strategies.

Pediatric Investigators Collaborative Network on Infections in Canada Study of Respiratory Syncytial Virus-associated Deaths in Pediatric Patients in Canada, 2003-2013.

Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are <0.5%, but up to 37% in patients with underlying medical conditions. The objective of this study was to characterize factors associated with deaths among children hospitalized with RSV infection in Canadian pediatric centers. A retrospective case series of children aged ≤18 years with RSV-associated deaths at centers affiliated with the Pediatric Investigators Collaborative Network on Infections in Canada from 2003–2013, inclusive, was performed [corrected]. Cases were identified using RSV-specific International Classification of Diseases codes to capture deaths where a diagnosis of RSV infection was present. Eleven centers reported 79 RSV-associated deaths. RSV was regarded as primarily responsible for death in 32 cases (40.5%). Median age at death was 11 months (range, <1 month to 16 years). Thirty-nine patients (49.4%) were male. Fourteen patients (17.7%) had no known risk factors for severe RSV infection. Healthcare-associated RSV infections (HAIs) accounted for 29 deaths (36.7%), with RSV judged to be the primary cause of death in 9 of these cases. RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs.

Quantification and determinants of the amount of respiratory syncytial virus (RSV) shed using real time PCR data from a longitudinal household study.

Background A better understanding of respiratory syncytial virus (RSV) epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR) assay. The amount of virus shed was quantified by calculating the 'area under the curve' using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2) log10 ribonucleic acid (RNA) copies. Young age(<1 year), presence of upper respiratory symptoms, intra-household acquisition of infection, an individual's first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.

Quantification and determinants of the amount of respiratory syncytial virus (RSV) shed using real time PCR data from a longitudinal household study

Background: A better understanding of respiratory syncytial virus (RSV) epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods: RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR) assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results: The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2) log 10 ribonucleic acid (RNA) copies * days. Young age (<1 year), presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions: The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.