Primary care physicians' perspectives on respiratory syncytial virus (RSV) disease in adults and a potential RSV vaccine for adults.

BACKGROUND: Deaths attributable to respiratory syncytial virus (RSV) among adults are estimated to exceed 11,000 annually, and annual adult hospitalizations for influenza and RSV may be comparable. RSV vaccines for older adults are in development. We assessed the following among primary care physicians (PCPs) who treat adults: (1) perception of RSV disease burden; (2) current RSV testing practices; and (3) anticipated barriers to adoption of an RSV vaccine. METHODS: We administered an Internet and mail survey from February to March 2017 to national networks of 930 PCPs. RESULTS: The response rate was 67% (620/930). Forty-nine percent of respondents (n = 303) were excluded from analysis as they reported never or rarely caring for an adult patient with possible RSV in the past year. Among respondents who reported taking care of RSV patients (n = 317), 73% and 57% responded that in patients ≥ 50 years, influenza is generally more severe than RSV and that they rarely consider RSV as a potential pathogen, respectively. Most (61%) agreed that they do not test for RSV because there is no treatment. The most commonly reported anticipated barriers to a RSV vaccine were potential out-of-pocket expenses for patients if the vaccine is not covered by insurance (93%) and lack of reimbursement for vaccination (74%). CONCLUSIONS: Physicians reported little experience with RSV disease in adults. They are generally not testing for it and the majority believe that influenza disease is more severe. Physicians will require more information about RSV disease burden in adults and the potential need for a vaccine in their adult patients.

Preclinical assessment of safety of maternal vaccination against respiratory syncytial virus (RSV) in cotton rats.

Maternal immunization directed to control RSV infection in newborns and infants is an appealing vaccination strategy currently under development. In this work we have modeled maternal vaccination against RSV in cotton rats (CR) to answer two fundamental questions on maternal vaccine safety. We tested (i), whether a known, unsafe RSV vaccine (i.e., FI-RSV Lot 100 vaccine) induces vaccine enhanced disease in the presence of passively transferred, RSV maternal immunity, and (ii) whether the same FI-RSV vaccine could induce vaccine enhanced disease in CR litters when used to immunize their RSV-primed mothers. Our data show that FI-RSV immunization of pups with subsequent RSV infection results in vaccine-enhanced disease independent of whether the pups were born to RSV-seropositive or RSV-seronegative mothers, and that FI-RSV immunization of RSV-seropositive mothers does not present a health risk to either the mother or the infant. Our study also raises a novel concern regarding infant immunization, namely that "safe" RSV vaccines (e.g., live RSV administered intramuscularly) may induce vaccine-enhanced disease in RSV-infected pups born to seropositive mothers. Finally, we describe for the first time a sharp decrease in RSV neutralizing antibody titers in immunized seropositive CR at the time of delivery. This decline may reflect maternal immune suppression, potentially pinpointing a window of increased vulnerability to RSV infection that could be alleviated by effective immunization of expectant mothers.

Estimating the burden of respiratory syncytial virus (RSV) on respiratory hospital admissions in children less than five years of age in England, 2007-2012.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of hospital admission in young children. With several RSV vaccines candidates undergoing clinical trials, recent estimates of RSV burden are required to provide a baseline for vaccine impact studies. OBJECTIVES: To estimate the number of RSV-associated hospital admissions in children aged <5 years in England over a 5-year period from 2007 using ecological time series modelling of national hospital administrative data. PATIENTS/METHODS: Multiple linear regression modelling of weekly time series of laboratory surveillance data and Hospital Episode Statistics (HES) data was used to estimate the number of hospital admissions due to major respiratory pathogens including RSV in children <5 years of age in England from mid-2007 to mid-2012, stratified by age group (<6 months, 6-11 months, 1-4 years) and primary diagnosis: bronchiolitis, pneumonia, unspecified lower respiratory tract infection (LRTI), bronchitis and upper respiratory tract infection (URTI). RESULTS: On average, 33 561 (95% confidence interval 30 429-38 489) RSV-associated hospital admissions in children <5 years of age occurred annually from 2007 to 2012. Average annual admission rates were 35.1 (95% CI: 32.9-38.9) per 1000 children aged <1 year and 5.31 (95% CI: 4.5-6.6) per 1000 children aged 1-4 years. About 84% (95% CI: 81-91%) of RSV-associated admissions were for LRTI. The diagnosis-specific burden of RSV-associated admissions differed significantly by age group. CONCLUSIONS: RSV remains a significant cause of hospital admissions in young children in England. Individual-level analysis of RSV-associated admissions is required to fully describe the burden by age and risk group and identify optimal prevention strategies.

RSV vaccine use--the missing data.

Respiratory syncytial virus (RSV) infection is the most important cause of hospitalization in infants and is one of the leading global causes of infant mortality and as such its prevention through vaccination is a public health priority. While essential for the successful implementation of vaccine programs, there remains a paucity of data on the epidemiology of the virus in different settings and age groups and limited knowledge about virus transmission and the health-care costs of the disease. Such data are now needed to populate health economic models and to inform optimal approaches to disease control through vaccination.

RSV vaccine in development: assessing the potential cost-effectiveness in the Dutch elderly population.

OBJECTIVES: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of morbidity, mortality and health-care utilization in the elderly population. A theoretical model was built to assess the levels of vaccine effectiveness and vaccine costs for which a hypothetical RSV-vaccine for Dutch elderly could be cost-effective. METHODS: Different vaccination strategies were evaluated by changing the levels of vaccine effectiveness and the willingness to pay per quality-adjusted life year gained (QALY). Outcome measures included direct medical costs, QALYs, life years gained, incremental cost-effectiveness ratios (ICERs) and the maximum total vaccination costs per individual (i.e. (vaccine price+administration costs)×nr of doses) while remaining cost-effective. RESULTS: Using base-case assumptions, it was estimated that vaccination of all persons 60 years and older would prevent 3402GP visits, 2989 antibiotic prescriptions, 535 hospitalizations and 249 deaths and would cost €73,261 per QALY, for a vaccine effectiveness of 70%. Vaccinating only the high risk population of 60 years and older would reduce the estimates to 2042GP visits, 2009 antibiotic prescriptions, 179 hospitalizations and 209 deaths and this reduced the cost per QALY to €34,796 per QALY. Using the same assumptions, the maximum total vaccination costs per individual ranged from €26 when vaccinating all persons 60 and older to €68 when vaccinating only persons aged 85 and above, using a willingness to pay threshold of €50,000 per QALY. For the high risk population aged 60 years and older the estimated maximum total vaccination costs ranged from €52 to €99. CONCLUSION: Vaccination of Dutch elderly against RSV was found cost-effective for several scenarios. As expected, vaccination is more likely to be cost-effective when only including persons who are at increased risk for contracting RSV or the potential complications of RSV. This theoretical study shows that based on the disease burden in the Dutch population aged 60yrs and older there is potential to develop a vaccine that might be considered cost-effective in the Netherlands.

A comparison of healthcare resource use for rotavirus and RSV between vulnerable children with co-morbidities and healthy children: a case control study.

OBJECTIVE: To quantify the differences in hospital length of stay (LOS) and cost between healthy and vulnerable children with cystic fibrosis (CF), insulin-dependent diabetes mellitus (IDDM), cancer, and epilepsy who contract rotavirus (RVGE) or respiratory syncytial virus (RSV). METHODS: Hospital Episode Statistics (HES) data were collected for England, for children <5 years old, admitted between April 2001 and March 2008, using ICD-10 codes for RVGE and RSV. Cases were identified as having RVGE and/or RSV plus CF, IDDM, cancer, or epilepsy. Healthy controls had RVGE and/or RSV only, additional controls had eczema only. Cost, hospital LOS, and demographics were collected. RESULTS: Four hundred and eighty-six (0.5%) cases and 101,784 (99.5%) healthy controls were admitted with RVGE or RSV, with 17,420 eczema controls. RVGE was present in 153 (31.5%) cases and 7532 (7.4%) healthy controls, and RSV in 333 (68.5%) cases and 94,252 (92.6%) healthy controls. Cases were older (1.1 years, SD = 1.3 years), had greater LOS (9.9 days, SD = 19.9), and cost more (£3477, SD = £7765) than healthy controls (age = 0.2, SD = 0.5, p < 0.001; LOS = 1.9 days, SD = 3.1, p < 0.001; cost = £595, SD = £727, p < 0.001). Cost for cases was 6-times greater than healthy controls (p < 0.001). Controls had a 0.3 day greater LOS (p < 0.001) with RSV, but a £17 (p = 0.085) lower mean cost than RVGE. CONCLUSION: RVGE and RSV are more serious diseases in vulnerable children, requiring more intense resource use. The importance of preventing infection in vulnerable children is underlined by hygiene and appropriate isolation and vaccination strategies. When universal vaccination is under consideration, as for rotavirus vaccines, evaluation of a vaccination programme should consider the potentially positive impact on vulnerable children. LIMITATIONS: Limitations of the study include a dependency on accurate coding, an expectation that patients are identified through laboratory testing, and the possibility of unidentified underlying conditions affecting the burden.

The use of health economics to guide drug development decisions: Determining optimal values for an RSV-vaccine in a model-based scenario-analytic approach.

Health-economic modelling is useful for assessing the clinical requirements and impact of new vaccines. In this study, we estimate the impact of potential vaccination for respiratory syncytial virus (RSV) of infants in the Netherlands. A decision analysis model was employed using seasonal data from a cohort of children (1996-1997 through 1999-2000) to assess hospitalisation, costs and impact of vaccination. Yearly, an estimated 3670 infants are hospitalised with RSV-infection in the Netherlands, vaccination protecting infants from 3 months of life onwards could prevent approximately 1000-3000 hospitalisations, depending on the effectiveness of the potential vaccine. Additionally, vaccination could prevent a major share of RSV-related costs. Comparison of the calculated break-even prices with the average price of recently introduced vaccines indicates that pricing for a potential RSV-vaccine most likely allows for only a single dose vaccination or several doses at a relatively low price per dose in order to achieve cost savings. However, if evidence on relevant RSV-related mortality would become available, higher pricing would be justified, while still remaining below accepted thresholds for cost-effectiveness.