Modelling the household-level impact of a maternal respiratory syncytial virus (RSV) vaccine in a high-income setting

Abstract Background Respiratory syncytial virus (RSV) infects almost all children by the age of 2 years, with the risk of hospitalisation highest in the first 6 months of life. Development and licensure of a vaccine to prevent severe RSV illness in infants is a public health priority. A recent phase 3 clinical trial estimated the efficacy of maternal vaccination at 39% over the first 90 days of life. Households play a key role in RSV transmission; however, few estimates of population-level RSV vaccine impact account for household structure. Methods We simulated RSV transmission within a stochastic, individual-based model framework, using an existing demographic model, structured by age and household and parameterised with Australian data, as an exemplar of a high-income country. We modelled vaccination by immunising pregnant women and explicitly linked the immune status of each mother-infant pair. We quantified the impact on children for a range of vaccine properties and uptake levels. Results We found that a maternal immunisation strategy would have the most substantial impact in infants younger than 3 months, reducing RSV infection incidence in this age group by 16.6% at 70% vaccination coverage. In children aged 3–6 months, RSV infection was reduced by 5.3%. Over the first 6 months of life, the incidence rate for infants born to unvaccinated mothers was 1.26 times that of infants born to vaccinated mothers. The impact in older age groups was more modest, with evidence of infections being delayed to the second year of life. Conclusions Our findings show that while individual benefit from maternal RSV vaccination could be substantial, population-level reductions may be more modest. Vaccination impact was sensitive to the extent that vaccination prevented infection, highlighting the need for more vaccine trial data.

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Disability-adjusted Life Years for respiratory syncytial virus in children under 2 years

10.21203/rs.3.rs-20260/v3 ◽

2020 ◽

Author(s):

jefferson buendia ◽

Fernando Polack ◽

Juana Patricia Sanchez Villamil

Keyword(s):

Respiratory Syncytial Virus ◽

Statistical Parameter ◽

Epidemiological Surveillance ◽

Years Of Life Lost ◽

Disability Adjusted Life Years ◽

Disability Adjusted Life ◽

Life Years ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Abstract BACKGROUND: Respiratory syncytial virus infection is the leading cause of bronchiolitis in Colombia. There is growing evidence about the impact of Respiratory syncytial virus on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years for respiratory syncytial virus in children under 2 years in ColombiaMETHODS: Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10000 iterations was used to estimate each statistical parameter using the package DALY calculator in R. RESULTS: In 2019, 260 873 years of life (CI95% 208 180- 347 023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16 – 27).CONCLUSION: This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies, such as RSV vaccination, to reduce morbidity associated with RSV infection should be encouraged in our country.

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Disability-adjusted Life Years for respiratory syncytial virus in Colombian children.

10.21203/rs.3.rs-20260/v1 ◽

2020 ◽

Author(s):

jefferson buendia ◽

Fernando Polack ◽

Juana Patricia Sanchez Villamil

Keyword(s):

Respiratory Syncytial Virus ◽

Statistical Parameter ◽

Epidemiological Surveillance ◽

Years Of Life Lost ◽

Disability Adjusted Life Years ◽

Disability Adjusted Life ◽

Life Years ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Abstract BACKGROUND Respiratory syncytial virus infection is the leading cause of bronchiolitis worldwide. However, little is known about the real impact of bronchiolitis on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years (1) in ColombiaMETHODS Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10000 iterations was used to estimate each statistical parameter using the package DALY calculator in R.RESULTS In 2019, 260 873 years of life (IC 95% 208 180–347 023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16–27).CONCLUSION This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies to reduce morbidity associated with RSV infection should be encouraged in our country.

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Disability-adjusted Life Years for respiratory syncytial virus in children under 2 years

10.21203/rs.3.rs-20260/v5 ◽

2020 ◽

Author(s):

Juana Patricia Sanchez Villamil ◽

Fernando Polack ◽

jefferson buendia

Keyword(s):

Respiratory Syncytial Virus ◽

Statistical Parameter ◽

Epidemiological Surveillance ◽

Years Of Life Lost ◽

Disability Adjusted Life Years ◽

Disability Adjusted Life ◽

Life Years ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Abstract BACKGROUND : Respiratory syncytial virus infection is the leading cause of bronchiolitis in Colombia. There is growing evidence about the impact of Respiratory syncytial virus on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years for respiratory syncytial virus in children under 2 years in Colombia METHODS : Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10000 iterations was used to estimate each statistical parameter using the package DALY calculator in R. RESULTS : In 2019, 260 873 years of life (CI95% 208 180- 347 023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16 – 27). CONCLUSION : This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies, such as RSV vaccination, to reduce morbidity associated with RSV infection should be encouraged in our country.

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Disability-adjusted Life Years for respiratory syncytial virus in children under 2 years

10.21203/rs.3.rs-20260/v4 ◽

2020 ◽

Author(s):

Juana Patricia Sanchez Villamil ◽

Fernando Polack ◽

Jefferson Buendia

Keyword(s):

Respiratory Syncytial Virus ◽

Statistical Parameter ◽

Epidemiological Surveillance ◽

Years Of Life Lost ◽

Disability Adjusted Life Years ◽

Disability Adjusted Life ◽

Life Years ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

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Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection

Scientific Reports ◽

10.1038/s41598-019-50217-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Abhijeet R. Sonawane ◽

Liang Tian ◽

Chin-Yi Chu ◽

Xing Qiu ◽

Lu Wang ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Principal Component ◽

Linear Interpolation ◽

Integrative Analysis ◽

Host Immune System ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Infections ◽

The Impact

Abstract Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known. We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection. We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection. We used RNA sequencing to interrogate the transcriptome of CD4+ T cells obtained from the same set of infants. After dimension reduction through principal component (PC) analysis, we performed an integrative analysis to identify significant co-variation between microbial clade and gene expression PCs. We then employed LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) to estimate the clade-gene association patterns for each infant. Our network-based integrative analysis identified several clade-gene associations significantly related to the severity of RSV infection. The microbial taxa with the highest loadings in the implicated clade PCs included Moraxella, Corynebacterium, Streptococcus, Haemophilus influenzae, and Staphylococcus. Interestingly, many of the genes with the highest loadings in the implicated gene PCs are encoded in mitochondrial DNA, while others are involved in the host immune response. This study on microbiome-transcriptome interactions provides insights into how the host immune system mounts a response against RSV and specific infectious agents in nasal microbiota.

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A Model of the Costs of Community and Nosocomial Pediatric Respiratory Syncytial Virus Infections in Canadian Hospitals

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2013/916769 ◽

2013 ◽

Vol 24 (1) ◽

pp. 22-26 ◽

Cited By ~ 3

Author(s):

Philip Jacobs ◽

Douglas Lier ◽

Katherine Gooch ◽

Katharina Buesch ◽

Michelle Lorimer ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Hospital Infection ◽

Sensitivity Analyses ◽

Base Case ◽

Infection Transmission ◽

Transmission Rates ◽

Hospitalization Costs ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

BACKGROUND: Approximately one in 10 hospitalized patients will acquire a nosocomial infection (NI) after admission to hospital, of which 71% are due to respiratory viruses, including the respiratory syncytial virus (RSV). NIs are concerning and lead to prolonged hospitalizations. The economics of NIs are typically described in generalized terms and specific cost data are lacking.OBJECTIVE: To develop an evidence-based model for predicting the risk and cost of nosocomial RSV infection in pediatric settings.METHODS: A model was developed, from a Canadian perspective, to capture all costs related to an RSV infection hospitalization, including the risk and cost of an NI, diagnostic testing and infection control. All data inputs were derived from published literature. Deterministic sensitivity analyses were performed to evaluate the uncertainty associated with the estimates and to explore the impact of changes to key variables. A probabilistic sensitivity analysis was performed to estimate a confidence interval for the overall cost estimate.RESULTS: The estimated cost of nosocomial RSV infection adds approximately 30.5% to the hospitalization costs for the treatment of community-acquired severe RSV infection. The net benefits of the prevention activities were estimated to be equivalent to 9% of the total RSV-related costs. Changes in the estimated hospital infection transmission rates did not have a significant impact on the base-case estimate.CONCLUSIONS: The risk and cost of nosocomial RSV infection contributes to the overall burden of RSV. The present model, which was developed to estimate this burden, can be adapted to other countries with different disease epidemiology, costs and hospital infection transmission rates.

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Temporal Dysbiosis of Infant Nasal Microbiota Relative to Respiratory Syncytial Virus Infection

10.1101/2020.04.30.071258 ◽

2020 ◽

Cited By ~ 1

Author(s):

Alex Grier ◽

Ann L. Gill ◽

Haeja A. Kessler ◽

Anthony Corbett ◽

Sanjukta Bandyopadhyay ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Disease ◽

Disease Severity ◽

Disease Risk ◽

Developmental Trajectory ◽

Microbiota Composition ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact ◽

Nasal Microbiota

ABSTRACTRationaleRespiratory Syncytial Virus (RSV) infection is a leading cause of infant respiratory disease and hospitalization. Infant airway microbiota occupying the nasopharynx have been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease severity and infection susceptibility, are not well understood.ObjectivesTo characterize associations between the nasal microbiota and RSV infection before, during, and after infants’ first respiratory illness.MethodsNasal 16S rRNA microbial community profiling of two cohorts of infants in the first year of life: 1) a cross-sectional cohort of 89 RSV infected infants sampled during illness and 102 population matched healthy controls, and 2) an individually matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled at time points before, during, and after infection.Measurements and Main ResultsWe identified 12 taxa significantly associated with RSV infection. All 12 were differentially abundant during infection, with seven differentially abundant prior to infection, and eight differentially abundant after infection. Eight of these taxa were associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs. infected than of disease severity.ConclusionsOur findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with first-time RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and the impact of RSV infection on microbiota composition. Identified taxa represent appealing targets for additional translationally-oriented research.

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Respiratory Syncytial Virus-Induced Activation and Migration of Respiratory Dendritic Cells and Subsequent Antigen Presentation in the Lung-Draining Lymph Node

Journal of Virology ◽

10.1128/jvi.00452-09 ◽

2009 ◽

Vol 83 (14) ◽

pp. 7235-7243 ◽

Cited By ~ 84

Author(s):

Michaël V. Lukens ◽

Debby Kruijsen ◽

Frank E. J. Coenjaerts ◽

Jan L. L. Kimpen ◽

Grada M. van Bleek

Keyword(s):

T Cells ◽

Lymph Node ◽

Respiratory Syncytial Virus ◽

Antigen Presentation ◽

Histocompatibility Complex ◽

Rsv Infection ◽

Draining Lymph Node ◽

Syncytial Virus ◽

And Migration ◽

The Impact

ABSTRACT In the respiratory tract, different dendritic cell (DC) populations guard a tight balance between tolerance and immunity to infectious or harmless materials to which the airways are continuously exposed. For infectious and noninfectious antigens administered via different routes, different subsets of DC might contribute during the induction of T-cell tolerance and immunity. We studied the impact of primary respiratory syncytial virus (RSV) infection on respiratory DC composition in C57BL/6 mice. We also tracked the migration of respiratory DC to the lymph nodes and studied antigen presentation by lung-derived and lymph node-resident DC to CD4+ and CD8+ T cells. We observed a massive influx of mainly CD103− CD11bhigh CD11c+ conventional DC (cDC) and plasmacytoid DC during the first 7 days of RSV infection, while CD103+ CD11blow CD11c+ cDC disappeared from the lung. The two major subsets of lung tissue DC, CD103+ CD11blow CD11c+ and CD103− CD11bhigh CD11c+ cDC, both transported RSV RNA to the lung-draining lymph node. Furthermore, these lung-derived cDC subsets as well as resident LN DC, which did not contain viral RNA, displayed viral antigen by major histocompatibility complex class I and class II to CD8+ and CD4+ T cells. Taken together, our data indicate that during RSV infections, at least three DC subsets might be involved during the activation of lymph node-homing naïve and memory CD4+ and CD8+ T cells.

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Disability-adjusted Life Years for respiratory syncytial virus in children under 2 years

10.21203/rs.3.rs-20260/v2 ◽

2020 ◽

Author(s):

jefferson buendia ◽

Fernando Polack ◽

Juana Patricia Sanchez Villamil

Keyword(s):

Respiratory Syncytial Virus ◽

Statistical Parameter ◽

Epidemiological Surveillance ◽

Years Of Life Lost ◽

Disability Adjusted Life Years ◽

Disability Adjusted Life ◽

Life Years ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Abstract BACKGROUND: Respiratory syncytial virus infection is the leading cause of bronchiolitis worldwide. However, little is known about the real impact of Respiratory syncytial virus on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years for respiratory syncytial virus in children under 2 years in Colombia METHODS: Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10000 iterations was used to estimate each statistical parameter using the package DALY calculator in R. RESULTS: In 2019, 260 873 years of life (CI95% 208 180- 347 023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16 – 27). CONCLUSION: This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies, such as RSV vaccination, to reduce morbidity associated with RSV infection should be encouraged in our country.

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Respiratory syncytial virus in young children: community cohort study integrating serological surveys, questionnaire and electronic health records, Born in Bradford cohort, England, 2008 to 2013

Eurosurveillance ◽

10.2807/1560-7917.es.2021.26.6.2000023 ◽

2021 ◽

Vol 26 (6) ◽

Author(s):

Ania Zylbersztejn ◽

Lucy Pembrey ◽

Harvey Goldstein ◽

Guy Berbers ◽

Rutger Schepp ◽

...

Keyword(s):

Cohort Study ◽

Respiratory Syncytial Virus ◽

Finite Mixture Models ◽

High Income ◽

Study Cohort ◽

Blood Samples ◽

Mortality And Morbidity ◽

Born In Bradford ◽

Rsv Infection ◽

Syncytial Virus

Background Bronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants. Aim To describe RSV epidemiology in children in the community in a high-income setting. Methods We used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records. We used finite mixture models to classify children as RSV infected/not infected according to their antibody concentrations at age 1 and 2 years. We assessed risk factors for primary RSV infection at each age using Poisson regression models. Results The study cohort included 700 children with cord blood samples; 490 had additional blood samples taken at both ages 1 and 2 years old. Of these 490 children, 258 (53%; 95% confidence interval (CI): 48–57%) were first infected with RSV at age 1, 99 of whom (38%; 95% CI: 33–43%) had been in contact with healthcare during peak RSV season (November–January). Having older siblings, birth in October–June and attending formal childcare were associated with risk of RSV infection in infancy. By age 2, a further 164 of 490 children (33%; 95% CI: 29–38%) had been infected. Conclusion Over half of children experienced RSV infection in infancy, a further one third had evidence of primary RSV infection by age 2, and one in seven remained seronegative by their second birthday. These findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes in high-income settings.

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