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Hospitalizations for respiratory syncytial virus (RSV) among adults in the United States, 1997 - 2012

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Background Respiratory syncytial virus (RSV) is an established cause of serious lower respiratory disease in children, but the burden in adults is less well studied. Methods We conducted a retrospective study of hospitalizations among adults ?20 years from the 1997-2012 National Inpatient Sample (NIS). Trends in RSV admissions were described relative to unspecified viral pneumonia admissions. Hospitalization severity indicators were compared among immunocompromised RSV, non-immunocompromised RSV, and influenza admissions. Results An estimated 28,237 adult RSV hospitalizations occurred, compared to 652,818 influenza hospitalizations; 34% were immunocompromised individuals. RSV and influenza patients had similar age, gender and race distributions, but RSV was more often diagnosed in urban teaching hospitals (73.0% for RSV vs. 34.6% for influenza) and large hospitals (71.9% vs. 56.4%). RSV hospitalization rates increased from 1997-2012, particularly for those ≥ 60, increasing from 0.5 to 4.6 per 100,000, while unspecified pneumonia admission rates decreased significantly (p<0.001). Immunocompromised patients with RSV hospitalization had significantly higher inpatient mortality (p=0.013), use of mechanical ventilation (p=0.016), mean length of stay (LOS) (p<0.001), and mean cost p<0.001) than non-immunocompromised RSV hospitalizations. Overall, RSV hospitalizations were more severe than influenza hospitalizations (6.2% mortality for RSV vs. 3.0% for influenza, 16.7% vs. 7.2% mechanical ventilation, mean LOS of 6.0 vs. 3.6 days, and mean cost of $38,828 vs. $14,519). Conclusions RSV hospitalizations in adults are increasing, likely due to increasing recognition and diagnosis. The burden of RSV in adults deserves attention. Although there are fewer hospitalizations than influenza, those that are diagnosed are on average more severe.
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© The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Hospitalizations for respiratory syncytial virus (RSV) among adults in the United States,
1997 2012
Susan T. Pastula1, Judith Hackett2, Jenna Coalson1, Xiaohui Jiang1, Tonya Villafana2,
Christopher Ambrose2, Jon Fryzek1
1Epidstat Institute, Ann Arbor, MI, USA
2AstraZeneca / Medimmune, Gaithersburg, MD, USA
Running head: Hospitalizations for RSV in the U.S.
Keywords: Respiratory syncytial virus; adult; hospitalizations
Corresponding Author: Susan T. Pastula, Epidstat Institute, 2100 Commonwealth, Suite 203,
Ann Arbor, MI 48105 (734) 929-9150.
Alternate corresponding Author: Judith Hackett, AstraZeneca, One MedImmune Way,
Gaithersburg, MD 20878 (301) 398-0500.
Keypoints: The incidence of RSV hospitalizations in adults is increasing, likely due to increasing
recognition and diagnosis. There are fewer hospitalizations than influenza, however when
diagnosed they are more severe.
Open Forum Infectious Diseases Advance Access published January 9, 2017
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Abstract
Background: Respiratory syncytial virus (RSV) is an established cause of serious lower
respiratory disease in children, but the burden in adults is less well studied.
Methods: We conducted a retrospective study of hospitalizations among adults ≥20 years from
the 1997-2012 National Inpatient Sample (NIS). Trends in RSV admissions were described
relative to unspecified viral pneumonia admissions. Hospitalization severity indicators were
compared among immunocompromised RSV, non-immunocompromised RSV, and influenza
admissions.
Results: An estimated 28,237 adult RSV hospitalizations occurred, compared to 652,818
influenza hospitalizations; 34% were immunocompromised individuals. RSV and influenza
patients had similar age, gender and race distributions, but RSV was more often diagnosed in
urban teaching hospitals (73.0% for RSV vs. 34.6% for influenza) and large hospitals (71.9% vs.
56.4%). RSV hospitalization rates increased from 1997-2012, particularly for those 60,
increasing from 0.5 to 4.6 per 100,000, while unspecified pneumonia admission rates decreased
significantly (p<0.001). Immunocompromised patients with RSV hospitalization had
significantly higher inpatient mortality (p=0.013), use of mechanical ventilation (p=0.016), mean
length of stay (LOS) (p<0.001), and mean cost p<0.001) than non-immunocompromised RSV
hospitalizations. Overall, RSV hospitalizations were more severe than influenza hospitalizations
(6.2% mortality for RSV vs. 3.0% for influenza, 16.7% vs. 7.2% mechanical ventilation, mean
LOS of 6.0 vs. 3.6 days, and mean cost of $38,828 vs. $14,519).
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Conclusions: RSV hospitalizations in adults are increasing, likely due to increasing recognition
and diagnosis. The burden of RSV in adults deserves attention. Although there are fewer
hospitalizations than influenza, those that are diagnosed are on average more severe.
Manuscript
Abbreviations
AHRQ Agency for Healthcare Research and Quality
BMT Bone marrow transplant
CI Confidence interval
COPD Chronic obstructive pulmonary disease
HCUP Healthcare Cost and Utilization Project
ICD-9(-CM) International Classification of Diseases, Ninth Revision, Clinical Modification
ILI Influenza-like Illness
LOS Length of stay
NIS National (Nationwide) Inpatient Sample
OR Odds ratio
RSV Respiratory syncytial virus
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Introduction
Respiratory syncytial virus (RSV) is well established as an important cause of serious lower
respiratory disease in children, but the burden in adults is less well studied. Outbreaks identified
in long-term care facilities in the late 1970s and early 1980s first drew attention to RSV as a
potential cause of serious respiratory disease in older adults [1]. Studies of adults have reported
the presence of RSV in 3% - 12% of patients hospitalized with respiratory symptoms [2-4]. RSV
has been confirmed in 1% to 8% of COPD exacerbations [5-10] and in 5% to 11% of adults
admitted with pneumonia, COPD, heart failure, or asthma [2]. More recent evidence suggests
that the burden of RSV-related illness among adults may approach or even exceed that of non-
pandemic influenza A [2, 11-16].
Older adults are at higher risk for severe morbidity due to RSV [1-3, 11, 16, 17]. From 1995-
2009 in the United Kingdom, Fleming found that older adults made up 79% of hospitalizations
for RSV and 93% of deaths from RSV [13]. The annual rate of disease caused by RSV in
patients over 65 years of age has been estimated to be between 3% and 7% [2, 18-20]. In an
influenza vaccine study of subjects 65 years and older conducted from 2008-2010, throat swabs
were tested from subjects with influenza-like illness (ILI). RSV was found in 7.4% of non-
hospitalized cases, and in 12.5% of hospitalizations for ILI [3].
Immunocompromised adults, such as bone marrow transplant (BMT) recipients, are also at
particularly high risk for severe RSV illness. A study of RSV in immunocompromised patients
reported an RSV-related mortality rate of 36% overall, and 50% in BMT patients [21]. In another
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study, mortality rates for BMT patients with RSV ranged from 30-70% [4]. RSV was diagnosed
in 15% of BMT recipients hospitalized for respiratory illnesses, which progressed to pneumonia
in 61% of these patients [22]. These studies suggest that significant morbidity and mortality can
occur in immunocompromised patients diagnosed with RSV, but more information is needed to
demonstrate the role and severity of RSV in adults for the U.S. healthcare system at large.
Inpatient hospital discharge data can be used to examine the importance of diagnosed RSV as a
factor in hospitalizations in adults over time and its association with other reported
comorbidities, and to contextualize these results with influenza as a more commonly recognized
cause of severe outcomes in adults with respiratory disease . Our study characterizes the trends
in hospitalizations attributed to RSV infections among adults 20 years or older in the United
States of America (US) from 1997 to 2012 using nationally representative inpatient hospital
discharge data. We compared severity indicators, including in-patient deaths, use of mechanical
ventilations, length of stay (LOS) and costs, among immunocompromised adults with RSV, non-
immunocompromised adults with RSV, and adults hospitalized for influenza.
Methods
A retrospective study of RSV hospitalizations among adults (≥20 years) was conducted using
discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization
Project (HCUP), Agency for Healthcare Research and Quality (AHRQ) for the years 1997 to
2012. The NIS is a nationally representative sample of hospital inpatient stays developed by the
HCUP and sponsored by the AHRQ. Data are contributed from the HCUP State Inpatient
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Databases (), http://www.hcup-us.ahrq.gov/db/hcupdatapartners.jspand include records for more
than seven million all-payer hospital stays each year [23].
NIS data contains up to 25 diagnostic codes for each hospitalization, based on the International
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM; hereafter, simply
ICD-9). During the study years, there were 3 RSV-specific ICD-9 codes: 480.1: Pneumonia due
to RSV; 466.11: Bronchiolitis due to RSV; and 079.6: RSV. Our analysis included all
hospitalizations occurring in adults ≥20 years of age with at least one of the three RSV-specific
ICD-9 codes listed in any diagnostic position in their hospitalization record.
Hospitalization rates for 1997-2012 were calculated using the weighted estimate of total number
of annual hospitalizations due to RSV relative to the U.S. population estimates from annual U.S.
Census data. To investigate rates by age, hospitalized individuals were categorized as 20 to 44
years, 45 to 59 years, or 60 years and older. Hospitalization rates were calculated as numbers of
cases per 100,000 for each age group by year.
We also analyzed rates of RSV compared to those of pneumonia virus unspecified, defined as
ICD-9 480.9). The objective was to understand whether any observed changes in RSV
hospitalization incidence were driven by changes in RSV diagnosis frequency or true disease
incidence.
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For comparison of disease burden, we also assessed adult hospitalizations for influenza, defined
as ICD-9 codes 487- 488. If a hospitalization had codes for both RSV and influenza, it was
counted toward both populations. To examine the burden of disease for RSV and influenza, we
compared distribution by hospital characteristics such as geographical area, hospital type (urban
teaching/urban non-teaching/rural) and bedsize, using definitions included in the NIS database
[23].
We analyzed disease severity using several indicators recorded in the NIS, including in-patient
mortality, length of stay (LOS), use of mechanical ventilation, and total cost. Costs were adjusted
to 2015 US dollars. These indicators were examined for the entire study period and by year in
order to examine potential time trends. To investigate any temporal bias effects, we repeated the
analyses of hospital characteristics and severity after restricting the data to only the three most
recent years. Because they were expected to experience differences in disease outcomes,
hospitalization records were classified as being in adults who were immunocompromised or not
based on an existing AHRQ algorithm based on ICD-9-CM diagnosis and procedure codes [24].
Individuals’ hospitalization records were classified as immunocompromised if they had at least
one of these qualifying diagnostic or procedural codes in any position.
All data management and statistical analyses for this study were carried out using SAS version
9.3 (SAS Institute Inc., Cary, NC, USA), with procedures that incorporated NIS-provided
weights to account for the structure of the sample survey data. There was no imputation of
missing values in any analysis. The temporal trend in incidence rates by age group was assessed
by Poisson regression. Logistic regression was used to examine temporal trends in mechanical
ventilation and in-patient mortality. Because lengths of hospitalization stay and total
hospitalization charges were not normally distributed, geometric means were calculated. Linear
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regression was used to test temporal trends in lengths of hospitalization stay and total
hospitalization charges.
Results
Patient Characteristics
A total of 28,237 RSV inpatient hospitalizations were identified in adults in the 1997 to 2012
NIS database, distributed as: 480.1: Pneumonia due to RSV (43.6%); 466.11: Bronchiolitis due
to RSV (11.4%); and 079.6: RSV (47.6%). 33.6% of RSV admissions were classified as
immunocompromised (Table 1). Overall, RSV hospitalizations were more common in those who
were 60 and older (57.8%), female (56.6%), and non-Hispanic white (60.8%). Non-
immunocompromised RSV patients were more often female (62.1%), but immunocompromised
RSV patients were less often female (45.7%). A higher proportion (80.7%) of adult RSV
hospitalizations occurred in the winter months between December and March than in the other 8
months of the year (data not shown). An association was observed between RSV hospitalization
and immunocompromised status.
Influenza was more commonly diagnosed in the NIS than was RSV: 652,818 influenza patients
were identified, nearly 23 times the number of RSV hospitalizations. The vast majority of
influenza cases were in patients that were not immunocompromised (89.7%), but the age, gender
and racial distributions of patients with influenza were not appreciably different than those of
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RSV (Table 1). 683 hospitalizations had both RSV and influenza diagnosis codes, equaling
2.4% of all RSV admissions and 0.1% of all influenza admissions.
149,433 admissions for Pneumonia, virus unspecified were identified between 1997-2012.
Patients with this diagnosis were more often 60 and older (55.5%), female (59.6%), and non-
Hispanic white (61.2%).
Hospital Characteristics
Both RSV and influenza hospitalizations were slightly more likely to be from the southern U.S.
than other regions of the country, and slightly less likely from the West (Table 2). RSV cases
were identified most often in urban teaching hospitals (73.0%), and large hospitals (71.9%) as
opposed to smaller facilities (9.9%). An even larger proportion of immunocompromised RSV
patients were diagnosed in urban teaching hospitals (88.8%) and large hospitals (80.5%). In
contrast, influenza hospitalizations were more evenly distributed between rural (26.2%), urban
nonteaching (39.2%), and urban teaching hospitals (34.6%). Immunocompromised influenza
patients were most often seen in urban teaching hospitals (51.1%), but those who were not
immunocompromised were commonly treated in urban nonteaching (39.6%) and urban teaching
(32.8%) hospitals. Pneumonia virus unspecified patients had similar distributions to influenza;
they were most often from the southern U.S. (37.4%). They were identified in urban non-
teaching hospitals most frequently (42.5%) and large hospitals (57.1%).
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Trends
Figure 1 shows the annual age-stratified RSV hospitalization rates per 100,000 persons. The rate
of RSV hospitalizations increased significantly for all ages between 1997 and 2012 (p<0.001),
most dramatically so for patients 60 years and older. The hospitalization rate in this group
increased by 8.6-fold from 0.54 to 4.64 per 100,000 over the 16-year period. In contrast to the
RSV rates, there was a significant decrease in pneumonia virus unspecified admissions among
those 60 and older in the same timeframe (Figure 2, p<0.001). Pneumonia virus unspecified
admission rates among 20-44 year olds and 45-59 year olds had non-significant decreases
(p=0.617 and p=0.622, respectively).
Indicators of Severity and Hospitalization Costs
Frequency of death increased with age, from 4.1% of 20-44 year olds with RSV to 6.2% of 45-59
year olds to 6.9% of inpatients 60 and older (Table 3). Thus, the majority of all RSV-related
deaths occurred amongst those 60 and older (63.8% = 1118/1751 total RSV deaths). However,
mechanical ventilation use, LOS, and costs were highest in 45-59 year olds. Compared to non-
immunocompromised patients, immunocompromised patients with RSV were more likely to die
during hospitalization (7.3% vs. 5.6%, p=0.013), had longer mean LOS (7.3 days vs. 5.4 days,
p<0.001), and had higher mean cost ($66,476 vs. $29,316, p<0.001), but were less likely to
receive mechanical ventilation (14.6% vs. 17.7%, p=0.016).
There were more than ten times as many in-hospital deaths with diagnoses of influenza
compared to RSV, but death occurred in only 3.0% of influenza hospitalizations and 3.6% of
pneumonia virus unspecified hospitalizations compared to 6.2% of RSV hospitalizations. The
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average length of stay for RSV was 6.0 days, compared to 3.6 days for influenza, and 4.3 days
for pneumonia virus unspecified. Relatedly, the mean adjusted costs for RSV hospitalizations
were higher ($38,828) than those for influenza ($14,519) or unspecified pneumonia ($18,051)
hospitalizations.
When more recent data (2010-2012) were examined separately, the patterns of severity were
similar to those observed in the full 16-year dataset (Supplemental Table 1). Recent RSV
hospitalizations had lower mortality than the full dataset (5.1% vs. 6.2%) but higher mechanical
ventilation use (17.5% vs 16.7%). Although the average LOS from 2010-2012 was slightly
shorter than the overall dataset (5.6 days vs. 6.0 days), the mean adjusted cost per case was
higher for recent RSV at $43,328, compared to $38,828. The higher severity of RSV versus
influenza hospitalizations was also present in 2010-2012, with higher frequency of mortality
(5.1% for RSV vs. 3.3% for influenza), more frequent use of mechanical ventilation (17.5% vs.
11.1%), longer LOS (5.6 vs. 3.6 days), and higher cost per hospitalizations ($43,328 vs.
$22,631).
Discussion
In our study of adults hospitalized for RSV, identified by use of ICD-9 codes, we found an
abrupt increase in the rate of hospitalizations of RSV starting approximately in 2007, especially
in older adults (≥60 years). We observed an overall decrease in rates of pneumonia virus
unspecified for this age group, which suggests that this pattern is due to increased recognition
(and diagnosis) of RSV as an important cause of disease in older adults rather than true increases
in incidence. This is also consistent with our observation that RSV was identified more often in
urban teaching hospitals than in smaller or rural hospitals, although this could also be related to
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transfer of complex cases to tertiary care centers, or due to molecular diagnostic testing being
more accessible in a teaching facility. As awareness and testing for RSV in adults continues to
increase, more effective treatments can be administered, likely limiting improper use of
antibiotics.
Although counts of diagnosed RSV hospitalizations in adults are still dwarfed by those of
influenza, individuals hospitalized with RSV had more severe illness compared to those
hospitalized with influenza. This observation of elevated severity is consistent with data from
other sources. A prospective study conducted between 1975-95 in healthy working-age adults
found the duration of RSV illness to be longer than that of influenza (9.5 days vs. 6.8 days) [25]
[19]. In our analysis, 16.7% of RSV hospitalizations required mechanical ventilation, similar to
a 2010 review which reported that 3.2 13% of adult RSV patients required assisted ventilation
[26]. As it is possible that more severe cases are more likely to be diagnosed, further evidence is
needed to confirm the degree of severity in RSV hospitalizations observed in this study as
diagnosis becomes more common, but the present findings suggest the importance of increased
awareness that RSV can be an important cause of disease in adults. These results also provide
further evidence that the risk of serious RSV disease is particularly high among
immunocompromised adults, consistent with previous observations [4, 21, 22] .
Our study methodology had several inherent limitations. Using ICD-9-coded administrative data
will underestimate RSV incidence, because these are the most symptomatic cases in the
community needing hospitalization. Not all hospitalizations receive diagnostic testing to identify
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the causal pathogen. The burden of RSV disease is particularly likely to be underestimated in
adults, because testing adult respiratory specimens for RSV is generally not standard practice.
Several authors have reported that RSV infections are rarely diagnosed in adults, in part because
available rapid antigen detection tests were insensitive in adults and because medical
practitioners rarely request tests for RSV for this age group [1, 17, 27]. The trend in increasing
diagnosis of RSV may have resulted from the development of improved sensitivity in diagnostic
testing in recent years, causing the demonstrated shift in cases from another respiratory diagnosis
to RSV.
While lack of diagnostic testing may have led to underestimation of the total number of
hospitalizations related to RSV, these codes are the most specific method of identifying RSV-
related hospitalizations in data based on ICD-9 codes alone. All diagnostic code positions were
used in order to prevent underestimations and biases related to variability in decisions about
diagnostic priority across regions and more than a decade of data.
The strength of this study lies in the size and quality of the database analyzed. The NIS database
is a representative sample of all hospitalizations in the U.S., so this analysis of the hospital
admissions for RSV, influenza and non-RSV pneumonia is generalizable to the total U.S.
population. Fifteen years of data provided the ability to look at trends across years, and allowed
us to analyze healthcare use patterns by geographic area, as well as hospital type and size.
Because of the large amount of data in the NIS, examining a relatively rarely reported disease
such as RSV is possible.
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Conclusion
RSV is a serious respiratory disease in children that is being increasingly recognized as a serious
cause of illness in adults. The incidence of diagnosed RSV hospitalizations, especially in older
adults, has increased significantly in the United States. As clinicians become more aware of and
diagnose more cases of RSV, rates may continue to climb. RSV hospitalizations appear to be
consistently more severe than influenza hospitalizations, especially for older adults and those
that are immunocompromised, with greater clinical and economic burden. RSV disease deserves
attention as a potentially severe cause of respiratory hospitalizations in adults.
Potential conflicts of interest
J.H., T.V., and C.A.. are shareholders in AstraZeneca / MedImmune. S.P., J.C., X.J., and J.F.
are consultants to AstraZeneca.
Funding
This work was supported by AstraZeneca.
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Table 1 - Characteristics of RSV patients, 1997-2012, compared to Influenza patients by Immunocompromised (IC) status and
Pneumonia virus unspecified
Characteristic
RSV n (%)
IC
RSV n (%)
Total
Influenza n (%)
IC
Influenza n (%)
Not IC
Influenza n (%)
Total
Pneumonia,
virus unspec. n
(%) Total
Total
9,483 (33.6%)
28,237 (100%)
66,944 (10.3%)
585,874 (89.7%)
652,818 (100%)
149,433 (100%)
Age (years)
20-44
2,157 (22.7%)
5,061 (17.9%)
12,705 (19.0%)
125,845 (21.5%)
138,549 (21.2%)
32,758 (21.9%)
45-59
3,208 (33.8%)
6,861 (24.3%)
16,510 (24.7%)
113,842 (19.4%)
130,352 (20.0%)
33,794 (22.6%)
60+
4,118 (43.4%)
16,316 (57.8%)
37,729 (56.4%)
346,188 (59.1%)
383,916 (58.8%)
82,882 (55.5%)
Gender
Male
5,147 (54.3%)
12,255 (43.4%)
35,634 (53.3%)
232,604 (39.7%)
268,238 (41.1%)
60,280 (40.4%)
Female
4,331 (45.7%)
15,977 (56.6%)
31,282 (46.7%)
353,060 (60.3%)
384,342 (58.9%)
89,109 (59.6%)
Race or ethnic group
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Characteristic
RSV n (%)
IC
RSV n (%)
Total
Influenza n (%)
IC
Influenza n (%)
Not IC
Influenza n (%)
Total
Pneumonia,
virus unspec. n
(%) Total
Non-Hispanic White
5,744 (60.6%)
17,157 (60.8%)
34,309 (51.3%)
339,918 (58.0%)
374,228 (57.3%)
91,406 (61.2%)
Non-Hispanic Black
1,209 (12.8%)
3,065 (10.9%)
10,447 (15.6%)
48,015 (8.2%)
58,462 (9.0%)
11,871 (7.9%)
Hispanic
735 (7.8%)
1,955 (6.9%)
5,623 (8.4%)
35,440 (6.0%)
41,063 (6.3%)
8,016 (5.4%)
Other or Unknown
1,794 (18.9%)
6,060 (21.5%)
16,564 (24.7%)
162,501 (27.7%)
179,065 (27.4%)
38,140 (25.5%)
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Table 2 - Hospital characteristics of RSV, 1997 2012, compared to Influenza by Immuncompromised status (IC) and
Pneumonia virus unspecified
Hospital
Characteristic
RSV n (%)
IC
RSV n (%)
Not IC
RSV n (%)
Total
Influenza n (%)
IC
Influenza n (%s)
Not IC
Influenza n (%)
Total
Pneumonia,
virus unspec.
n (%)
Total
Total
9,483 (33.6%)
18,754 (66.4%)
28,237 (100%)
66,944 (10.3%)
585,874 (89.7%)
652,818 (100%)
149,433 (100%)
Region
NE
1,954 (22.7%)
4,527 (26.3%)
6,481 (25.1%)
11,382 (18.2%)
89,130 (15.9%)
100,512 (16.1%)
20,721 (14.4%)
Midwest
2,041 (23.7%)
4,841 (28.1%)
6,882 (26.6%)
18,462 (29.5%)
174,603 (31.1%)
193,065 (30.9%)
37,056 (25.7%)
South
2,639 (30.6%)
4,610 (26.8%)
7,249 (28.1%)
22,001 (35.2%)
215,460 (38.4%)
237,461 (38.1%)
54,028 (37.4%)
West
1,983 (23.0%)
3,247 (18.9%)
5,231 (20.2%)
10,684 (17.1%)
82,267 (14.7%)
92,951 (14.9%)
32,582 (22.6%)
Location
Rural
126 (1.5%)
1,615 (9.5%)
1,741 (6.8%)
8,536 (13.7%)
154,446 (27.6%)
162,982 (26.2%)
33,010 (23%)
Urban
832 (9.7%)
4,336 (25.4%)
5,168 (20.2%)
21,901 (35.2%)
221,756 (39.6%)
243,657 (39.2%)
61,093 (42.5%)
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nonteaching
Urban
teaching
7,612 (88.8%)
11,091 (65.1%)
18,703 (73.0%)
31,806 (51.1%)
183,351 (32.8%)
215,157 (34.6%)
49,672 (34.5%)
Bedsize
Small
503 (5.9%)
2,043 (12.0%)
2,546 (9.9%)
7,400 (11.9%)
105,106 (18.8%)
112,506 (18.1%)
22,419 (15.6%)
Medium
1,171 (13.7%)
3,477 (20.4%)
4,648 (18.1%)
12,950 (20.8%)
145,675 (26.0%)
158,625 (25.5%)
39,279 (27.3%)
Large
6,896 (80.5%)
11,523 (67.6%)
18,419 (71.9%)
41,892 (67.3%)
308,772 (55.2%)
350,664 (56.4%)
82,076 (57.1%)
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Table 3 - Indicators of Severity for RSV Hospitalizations, 1997-2012, compared to Influenza hospitalizations by
Immuncompromised (IC) status and Pneumonia virus unspecified
Severity Indicator
RSV n (%)
IC
RSV n (%)
Not IC
RSV n (%)
Total
Influenza n
(%)
IC
Influenza n
(%)
Not IC
Influenza n (%)
Total
Pneumonia virus
unspec. n (%)
Total
Total Hospitalizations
9,483
(33.6%)
18,754
(66.4%)
28,237
(100%)
66,944 (10.3%)
585,874
(89.7%)
652,818 (100%)
149,433 (100%)
Died during
hospitalization
695 (7.3%)
1,056 (5.6%)
1,751 (6.2%)
3,833 (5.7%)
15,873 (2.7%)
19,706 (3.0%)
5359 (3.6%)
Age 20-44
139 (6.4%)
71 (2.4%)
210 (4.1%)
507 (4.0%)
1,519 (1.2%)
2,026 (1.5%)
514 (1.6%)
Age 45-59
267 (8.3%)
156 (4.3%)
423 (6.2%)
923 (5.6%)
2,321 (2.0%)
3,244 (2.5%)
706 (2.1%)
Age 60+
289 (7.0%)
828 (6.8%)
1,118 (6.9%)
2,402 (6.3%)
12,033 (3.5%)
14,436 (3.8%)
4,139 (5.0%)
Mechanical ventilation use
1,389
(14.6%)
3,319 (17.7%)
4,708 (16.7%)
7,899 (11.8%)
38,877 (6.6%)
46,777 (7.2%)
13,449 (9.0%)
Age 20-44
262 (12.1%)
452 (15.6%)
714 (14.1%)
1,380 (10.9%)
8,131 (6.5%)
9,510 (6.9%)
3,127 (9.5%)
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Age 45-59
469 (14.6%)
810 (22.2%)
1,279 (18.6%)
2,475 (15.0%)
10,655 (9.4%)
13,130 (10.1%)
3,670 (10.9%)
Age 60+
657 (16.0%)
2,058 (16.9%)
2,715 (16.6%)
4,045 (10.7%)
20,092 (5.8%)
24,137 (6.3%)
6,652 (8.0%)
Length of stay (days)1
7.3
5.4
6.0
4.8
3.5
3.6
4.3
Age 20-44
7.4
4.6
5.6
4.1
2.6
2.7
3.6
Age 45-59
7.5
5.3
6.2
4.8
3.3
3.5
4.2
Age 60+
7.1
5.6
6.0
5.1
4.0
4.1
4.7
Adjusted cost ($)1
66,476.1
29,316.2
38,827.6
25,198.5
13,634.9
14,519.1
18,051.2
Age 20-44
71,822.3
27,021.1
41,202.0
24,070.5
11,831.5
12,627.4
16,950.0
Age 45-59
73,896.5
33,196.5
48,431.2
29,294.9
14,761.9
16,098.0
19,473.9
Age 60+
58,648.8
28,785.8
34,609.1
23,958.1
13,985.2
14,742.5
17,940.8
1 Geometric mean
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Figure 1 Trends in RSV Hospitalization Rates by Year and Age group, 1997 - 2012
Figure 2 Trends in Pneumonia, virus unspecified (ICD 480.9) by Year and Age Group,
1997-2012
Figure 1
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Figure 2
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Supplementary resource (1)

... Recent studies have suggested that the occurrence of RSV infections in adults has been substantially underscored [13,14,[55][56][57][58], but limited data exist on the clinical characteristics of infections in pregnant women [45,47]. For instance, in a previous case series from the USA, two out of three cases eventually developed respiratory distress, requiring mechanical ventilation, suggesting that RSV infections in pregnancy may represent a clinically significant event [45]. ...
Article
Full-text available
Human Respiratory Syncytial Virus (RSV) is a highly contagious viral pathogen. In infants, it is usually listed among the main causes of medical referrals and hospitalizations, particularly among newborns. While waiting for the results of early randomized controlled trials on maternal vaccination against RSV, the present systematic review and meta-analysis aimed to collect available evidence on maternal RSV infections. According to the PRISMA statement, Pubmed, Embase, and pre-print archive medRxiv.og were searched for eligible studies published up to 1 April 2022. Raw data included the incidence of RSV infection among sampled pregnant women, and the occurrence of complications. Data were then pooled in a random-effects model. Heterogeneity was assessed using the I2 measure, while reporting bias was assessed by means of funnel plots and regression analysis. A total of 5 studies for 282,918 pregnancies were retrieved, with a pooled prevalence of 0.2 per 100 pregnancies and 2.5 per 100 pregnancies with respiratory tract infections. Neither maternal deaths nor miscarriages were reported. Even though detailed data were available only for 6309 pregnancies and 33 RSV cases, infant outcomes such as low birth weight and preterm delivery were rare (in both cases 0.04%), but up to 9.1% in cases where RSV diagnosis was confirmed. No substantially increased risk for preterm delivery (RR 1.395; 95%CI 0.566 to 3.434) and giving birth to a low-birth-weight infant (RR 0.509; 95%CI 0.134 to 1.924) was eventually identified. Conclusions. Although RSV is uncommonly detected among pregnant women, incident cases were associated with a relatively high share of complications. However, heterogeneous design and the quality of retrieved reports stress the need for specifically designed studies.
... In-hospital mortality rates were not significantly different between patients with RSV (12.1%) and those with influenza (14.3%), and were similar to those found in previous studies ( Falsey et al., 2005 ;Lee et al., 2013 ;Loubet et al., 2017 ). However, some studies have reported higher mortality rates in RSV patients than in those with influenza ( Cohen et al., 2019 ;Kestler et al., 2018 ;Kwon et al., 2017 ;Pastula et al., 2017 ). These findings confirm that adult patients with RSV infection have a mortality rate at least as high as patients with influenza infection. ...
Article
Full-text available
Introduction RSV is increasingly recognized in adults. An improved understanding of clinical manifestations and complications may facilitate diagnosis and management. Methods This was a retrospective study of hospitalized patients aged ≥ 18 years with RSV or influenza infection at Siriraj hospital, Thailand between January 2014 and December 2017. Results RSV and/or influenza were detected by RT-PCR in 570 (20.1%) of 2836 patients. After excluding patients coinfected with influenza A and B (n = 5), and with influenza and RSV (n = 3), 141 (5.0%) RSV and 421 (14.8%) influenza patients were analyzed. Over the study period, RSV circulated during the rainy season and peaked in September or October. Patients with RSV were older than patients with influenza and presented significantly less myalgia and fever, but more wheezing. Pneumonia was the most common complication, occurring in 110 (78.0%) of RSV cases and in 295 (70.1%) of influenza cases (p = 0.069). Cardiovascular complications were found in 30 (21.3%) RSV and 96 (22.8%) influenza (p = 0.707), and were reasons for admission in 15 (10.6%) RSV and 50 (11.9%) influenza. The in-hospital mortality rates for RSV (17; 12.1%) and influenza (60; 14.3%) were similar (p = 0.512). Conclusions In Thailand, RSV is a less common cause of adult hospitalization than influenza, but pulmonary and cardiovascular complications, and mortality are similar. Clinical manifestations cannot reliably distinguish between RSV and influenza infection; laboratory-confirmed diagnosis is needed.
Article
Background: Adult respiratory syncytial virus (RSV) vaccines are in the late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making. Methods: We performed a systematic review and meta-analysis of studies describing the incidence of medically attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab reverse transcription polymerase chain reaction (RT-PCR) results with paired serology (4-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum). Results: We identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100 000 adults ≥65 years of age was 178 (95% CI, 152‒204; n = 8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95% CI, 0‒319; n = 2) emergency department (ED) admissions, and 1519 (95% CI, 1109‒1929; n = 3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100 000 adults age ≥65 years were 267 hospitalizations (uncertainty interval [UI], 228‒306; prospective: 282; model-based: 236), 200 ED admissions (UI, 0‒478), and 2278 outpatient visits (UI, 1663‒2893). Persons <65 years with chronic medical conditions were 1.2-28 times more likely to be hospitalized for RSV depending on risk condition. Conclusions: The true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public health impact.
Article
Background Numerous studies in the U.S. have made estimates of the RSV burden among adults that vary widely due to differences in methodology, reliance on influenza surveillance, which does not adequately capture all RSV clinical symptoms, and lack of diagnostic methods to identify RSV when viral loads are low. Nevertheless, accurate burden estimates can inform healthcare planning, resource allocation and potentially, RSV vaccine policy. Methods A simple method combined with statewide and local hospitalization, medical record and U.S. Census data were used to estimate population-based RSV hospitalization burden among adults ages 18–64 years, ≥65 years, and including immunocompetent, immunocompromised and pregnant individuals during 2015–2018 for Allegheny County, Pennsylvania. Economic burden of hospitalization was estimated using state-provided average hospitalization charges for comparisons across patient groups. Results The largest burden was borne by adults ≥ 65 years of age whose rates per 100,000 population of that age group (939/100,000) were 7.0–9.0 times those of adults 18–64 years of age (118/100,000). Immunosuppressed patients bore the greatest relative burden of RSV hospitalizations (1,288–1,562/100,000 immunosuppressed individuals). RSV burden ranged from 0 to 808/100,000 pregnant women. Average total charges for RSV hospitalization in Allegheny County across all adults increased from $39 million in 2015–2016 to $57 million in 2016–2017 to $89 million in 2017–2018, due to both increased average charges for an acute respiratory hospitalization and increased numbers of RSV cases. Conclusions These RSV burden estimates add to the body of knowledge to guide public health policy makers and offer a method for simply and easily producing population-based burden estimates.
Article
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Background and aims: The burden of respiratory syncytial virus (RSV) infection in adults is of growing concern. This study was designed to quantify disease burden, treatment approaches, and outcomes associated with RSV infections in adult subpopulations, from prehospitalization to hospital discharge. Methods: A retrospective chart analysis was conducted to collect patient-case data from hospitalized US adults (aged >18 years) with RSV infection during two RSV seasons. Patients were categorized into risk groups: comorbid lung disease, immunocompromised, older adults (aged ≥65 years), and other adults (aged <65 years). Physicians reported diagnosis, treatment choices including respiratory supportive therapy (oxygen and fluid supplementation), and outcome variables using a standardized online case form. Results: The majority (277/379; 73%) of patients presented to the emergency room, with a mean age of 60 years. Once hospitalized, the median length of stay was 6.0 days (3.0-9.0), with disease severity having the greatest impact on duration of stay. No significant between-group differences in rates of patients requiring management in intensive care units were found (comorbid lung disease, 28%; immunocompromised, 36%; older adults, 26%; and other adults, 23%). Overall, respiratory supportive therapy was the most commonly used form of treatment. Antibiotics were administered in over half of all risk groups (comorbid lung disease, 61%; immunocompromised, 59%; older adults, 59%; and other adults, 51%). Patients usually required follow-up visits following discharge, with 10%-16% requiring skilled nursing care and approximately 25% requiring assistance from a social worker. Conclusion: RSV in adult subpopulations, irrespective of age, is a significant burden to healthcare systems.
Article
Background Respiratory syncytial virus (RSV) is an important cause of lower respiratory infections and hospitalizations among older adults. We aimed to estimate the potential clinical benefits and economic value of RSV vaccination of older adults in the United States (US). Methods We developed an economic model using a decision-tree framework to capture outcomes associated with RSV infections in US adults aged ≥ 60 years occurring during one RSV season for a hypothetical vaccine versus no vaccine. Two co–base-case epidemiology sources were selected from a targeted review of the US literature: a landmark study capturing all RSV infections and a contemporary study reporting medically attended RSV that also distinguishes mild from moderate-to-severe disease. Both base-case analyses used recent data on mortality risk in the year after RSV hospitalizations. Direct medical costs and quality-adjusted life-years (QALYs) lost per case were obtained from the literature and publicly available sources. Model outcomes included the population-level clinical and economic RSV disease burden among older adults, potential vaccine-avoidable disease burden, and the potential value-based price of a vaccine from a third-party payer perspective. Results Our two base-case analyses estimated that a vaccine with 50% efficacy and coverage matching that of influenza vaccination would prevent 43,700–81,500 RSV hospitalizations and 8,000–14,900 RSV-attributable deaths per RSV season, resulting in 1,800–3,900 fewer QALYs lost and avoiding $557-$1,024 million. Value-based prices for the co–base-case analyses were $152-$299 per vaccination at a willingness to pay of $100,000/QALY gained. Sensitivity analyses found that the economic value of vaccination was most sensitive to RSV incidence and increased posthospitalization mortality risks. Conclusions Despite variability and gaps in the epidemiology literature, this study highlights the potential value of RSV vaccination for older adults in the US. Our analysis provides contemporary estimates of the population-level RSV disease burden and insights into the economic value drivers for RSV vaccination.
Article
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Background Respiratory syncytial virus (RSV) is understood to be a cause of significant disease in older adults and children. Further analysis of RSV in younger adults may reveal further insight into its role as an important pathogen in all age groups. Methods We identified, through laboratory data, adults who tested positive for either influenza or RSV between January 2017 and June 2019 at a single Australian hospital. We compared baseline demographics, testing patterns, hospitalisations and outcomes between these groups. Results Of 1128 influenza and 193 RSV patients, the RSV cohort was older (mean age 54.7 vs. 64.9, p < 0.001) and was more comorbid as determined by the Charlson Comorbidity Index (2.4 vs. 3.2, p < 0.001). For influenza hospitalisations, the majority admitted were aged under 65 which was not the case for RSV (61.8% vs. 45.6%, p < 0.001). Testing occurred later in RSV hospitalisations as measured by the proportion tested in the emergency department (ED) (80.3% vs. 69.2%, p < 0.001), and this was strongly associated with differences in presenting phenotype (the presence of fever). RSV was the biggest predictor of 6-month representation, with age and comorbidities predicting this less strongly. Conclusion RSV is a significant contributor to morbidity and hospitalisation, sometimes outweighing that of influenza, and is not limited to elderly cohorts. Understanding key differences in the clinical syndrome and consequent testing paradigms may allow better detection and potentially treatment of RSV to reduce individual morbidity and health system burden. This growing area of research helps quantify the need for directed therapies for RSV.
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Background Respiratory syncytial virus (RSV) infections are common in adults, but data describing the cost of RSV-associated hospitalization are lacking due to inconsistency in diagnostic coding and incomplete case ascertainment. We evaluated costs of RSV-associated hospitalization in adult patients with laboratory-confirmed, community-onset RSV. Methods We included adults ≥ 18 years of age admitted to three hospital systems in New York during two RSV seasons who were RSV-positive by polymerase chain reaction (PCR) and had more than or equal to two acute respiratory infection symptoms or exacerbation of underlying cardiopulmonary disease. We abstracted costs from hospital finance systems or converted hospital charges to cost using cost-charge ratios. We converted cost into 2020 US dollars and extrapolated to the United States. We used a generalized linear model to determine predictors of hospitalization cost, stratified by admission to intensive care units (ICU). Results Cost data were available for 79% (601/756) of eligible patients. The mean total cost of hospitalization was $8403 (CI95 $7240–$9741). The highest costs were those attributed to ICU services $7885 (CI95 $5877–$10,240), whereas the lowest were radiology $324 (CI95 $275–$376). Other than longer length of stay, predictors of higher cost included having chronic liver disease (odds ratio [OR] 1.38 [CI95 1.05–1.80]) for patients without ICU admission and antibiotic use (OR 1.49 [CI95 1.10–2.03]) for patients with ICU admission. The annual US cost was estimated to be $1.2 (CI95 0.9–1.4) billion. Conclusion The economic burden of RSV hospitalization of adults ≥ 18 years of age in the United States is substantial. RSV vaccine programs may be useful in reducing this economic burden.
Article
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Article
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Information on respiratory viruses in subtropical region is limited. Incidence, mortality, and seasonality of influenza (Flu) A/B, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza viruses (PIV) 1/2/3 in hospitalized patients were assessed over a 15-year period (1998–2012) in Hong Kong. Male predominance and laterally transversed J-shaped distribution in age-specific incidence was observed. Incidence of Flu A, RSV, and PIV decreased sharply from infants to toddlers; whereas Flu B and ADV increased slowly. RSV conferred higher fatality than Flu, and was the second killer among hospitalized elderly. ADV and PIV were uncommon, but had the highest fatality. RSV, PIV 2/3 admissions increased over the 15 years, whereas ADV had decreased significantly. A “high season,” mainly contributed by Flu, was observed in late-winter/early-spring (February–March). The “medium season” in spring/summer (April–August) was due to Flu and RSV. The “low season” in late autumn/winter (October–December) was due to PIV and ADV. Seasonality varied between viruses, but predictable distinctive pattern for each virus existed, and temperature was the most important associating meteorological variable. Respiratory viruses exhibit strong sex- and age-predilection, and with predictable seasonality allowing strategic preparedness planning. Hospital-based surveillance is crucial for real-time assessment on severity of new variants.
Article
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Background: Growing evidence suggests respiratory syncytial virus (RSV) is an important cause of respiratory disease in adults. However, the adult burden remains largely uncharacterized as most RSV studies focus on children, and population-based studies with laboratory-confirmation of infection are difficult to implement. Indirect modelling methods, long used for influenza, can further our understanding of RSV burden by circumventing some limitations of traditional surveillance studies that rely on direct linkage of individual-level exposure and outcome data. Methods: Multiple linear time-series regression was used to estimate RSV burden in the United Kingdom (UK) between 1995 and 2009 among the total population and adults in terms of general practice (GP) episodes (counted as first consultation ≥28 days following any previous consultation for same diagnosis/diagnostic group), hospitalisations, and deaths for respiratory disease, using data from Public Health England weekly influenza/RSV surveillance, Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics. The main outcome considered all ICD-listed respiratory diseases and, for GP episodes, related symptoms. Estimates were adjusted for non-specific seasonal drivers of disease using secular cyclical terms and stratified by age and risk group (according to chronic conditions indicating severe influenza risk as per UK recommendations for influenza vaccination). Trial registration NCT01706302 . Registered 11 October 2012. Results: Among adults aged 18+ years an estimated 487,247 GP episodes, 17,799 hospitalisations, and 8,482 deaths were attributable to RSV per average season. Of these, 175,070 GP episodes (36 %), 14,039 hospitalisations (79 %) and 7,915 deaths (93 %) were in persons aged 65+ years. High- versus low-risk elderly were two-fold more likely to have a RSV-related GP episode or death and four-fold more likely be hospitalised for RSV. In most seasons since 2001, more GP episodes, hospitalisations and deaths were attributable to RSV in adults than to influenza. Conclusion: RSV is associated with a substantial disease burden in adults comparable to influenza, with most of the hospitalisation and mortality burden in the elderly. Treatment options and measures to prevent RSV could have a major impact on the burden of RSV respiratory disease in adults, especially the elderly.
Article
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Background Bronchiolitis caused by the respiratory syncytial virus (RSV) and its related complications are common in infants born prematurely, with severe congenital heart disease, or bronchopulmonary dysplasia, as well as in immunosuppressed infants. There is a rich literature on the different aspects of RSV infection with a focus, for the most part, on specific risk populations. However, there is a need for a systematic global analysis of the impact of RSV infection in terms of use of resources and health impact on both children and adults. With this aim, we performed a systematic search of scientific evidence on the social, economic, and health impact of RSV infection.MethodsA systematic search of the following databases was performed: MEDLINE, EMBASE, Spanish Medical Index, MEDES-MEDicina in Spanish, Cochrane Plus Library, and Google without time limits. We selected 421 abstracts based on the 6,598 articles identified. From these abstracts, 4 RSV experts selected the most relevant articles. They selected 65 articles. After reading the full articles, 23 of their references were also selected. Finally, one more article found through a literature information alert system was included.ResultsThe information collected was summarized and organized into the following topics: 1. Impact on health (infections and respiratory complications, mid- to long-term lung function decline, recurrent wheezing, asthma, other complications such as otitis and rhino-conjunctivitis, and mortality; 2. Impact on resources (visits to primary care and specialists offices, emergency room visits, hospital admissions, ICU admissions, diagnostic tests, and treatments); 3. Impact on costs (direct and indirect costs); 4. Impact on quality of life; and 5. Strategies to reduce the impact (interventions on social and hygienic factors and prophylactic treatments).Conclusions We concluded that 1. The health impact of RSV infection is relevant and goes beyond the acute episode phase; 2. The health impact of RSV infection on children is much better documented than the impact on adults; 3. Further research is needed on mid- and long-term impact of RSV infection on the adult population, especially those at high-risk; 4. There is a need for interventions aimed at reducing the impact of RSV infection by targeting health education, information, and prophylaxis in high-risk populations.
Article
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Background Influenza and respiratory syncytial virus (RSV) cause substantial mortality from respiratory and other causes in the USA, especially among people aged 65 and older. Objectives We estimated the influenza-attributable mortality and RSV-attributable mortality in the USA, stratified by age and risk status, using outcome definitions with different sensitivity and specificity. Methods Influenza- and RSV-associated mortality was assessed from October 1997-March 2009 using multiple linear regression modeling on data obtained from designated government repositories. ResultsThe main outcomes and measures included mortality outcome definitionspneumonia and influenza, respiratory broad, and cardiorespiratory disease. A seasonal average of 10682 (2287-16363), 19100 (4862-29245), and 28169 (6797-42316) deaths was attributed to influenza for pneumonia and influenza, respiratory broad, and cardiorespiratory outcome definitions, respectively. Corresponding values for RSV were 6211 (4584-8169), 11300 (8546-14244), and 17199 (13384-21891), respectively. A/H3N2 accounted for seasonal average of 71% influenza-attributable deaths; influenza B accounted for most (51-95%) deaths during four seasons. Approximately 70% influenza-attributable deaths occurred in individuals75years, with increasing mortality for influenza A/H3N2 and B, but not A/H1N1. In children aged 0-4years, an average of 97 deaths was attributed to influenza (A/H3N2=49, B=33, A/H1N1=15) and 165 to respiratory broad outcome definition (RSV). Influenza-attributable mortality was 294-fold higher in high-risk individuals. Conclusions Influenza-attributable mortality was highest in older and high-risk individuals and mortality in children was higher than reported in passive Centers for Disease Control and Prevention surveillance. Influenza B-attributable mortality was higher than A in four of 12 seasons. Our estimates represent an updated assessment of influenza-attributable mortality in the USA.
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