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Trends in Chronologic Age and Infant Respiratory Syncytial Virus Hospitalization: an 8-Year Cohort Study

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  • EpidStat Institute

Abstract

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children and the leading cause of hospitalization in infants aged <1 year. We examined trends in RSV hospitalization (RSVH) among infants from 1998 to 2006, using the United States (US) National Hospital Discharge Survey (NHDS) database. RSVH was defined by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 079.6 (RSV), 466.11 (acute bronchiolitis due to RSV), and 480.1 (pneumonia due to RSV). Age at the time of hospitalization was determined using NHDS birth records; RSVH rates were analyzed for infants grouped into three age cohorts (<3 months, 3 to 6 months, and >6 to <24 months). Trends in hospitalization rates were evaluated using linear regression. Relative rates (RR) and 95% confidence intervals (CI) were computed to compare average RSVH rates for infants across age-specific groups. The annual proportion of RSVH by age group was also calculated. Approximately 1.1 million (90,000-147,000 per year) RSVHs in predominantly term children aged <24 months were analyzed. Compared with children aged >6 to <24 months, rates for RSVH were significantly higher among infants aged <3 months (RR, 7.38; 95% CI, 7.35-7.41) and infants aged 3 to 6 months (RR, 5.28; 95% CI, 5.26-5.29). The proportion of RSVH in the first year of life was lowest among infants aged <1 month (9%). [corrected] The greatest proportion of RSVH was observed in children aged 3 to 6 months (14%-23% RSVH per year; chi-square P<0.0001). When the definition of RSVH was expanded to include unspecified hospitalizations for acute bronchiolitis, similar results were observed. RRs were highest among the <3- month and 3- to 6-month age groups. The highest proportion of RSVH was among the 3- to 6-month age group. Analysis of the impact of RSV season, clinical practices, and other factors on these trends is warranted.
Jon P. Fryzek · William J. Martone · Jessie R. Groothuis ()
One MedImmune Way, Gaithersburg, MD 20878, USA.
Email: GroothuisJ@MedImmune.com
Adv Ther (2011) 28(3)
DOI 10.1007/s12325-010-0106-6
ORIGINAL RESEARCH
Trends in Chronologic Age and Infant Respiratory
Syncytial Virus Hospitalization: an 8-Year Cohort Study
Jon P. Fryzek · William J. Martone · Jessie R. Groothuis
Received: September 29, 2010 / Published online: 7 February, 2011
© The Author(s) 2011. This article is published with open access at Springerlink.com
ABSTRACT
Introduction: Respiratory syncytial virus
(RSV) is a major cause of lower respiratory
tract infections in infants and young children
and the leading cause of hospitalization in
infants aged <1 year. Methods: We examined
trends in RSV hospitalization (RSVH) among
infants from 1998 to 2006, using the United
States (US) National Hospital Discharge Survey
(NHDS) database. RSVH was defined by the
International Classification of Diseases, 9th
Revision, Clinical Modification (ICD-9-CM)
codes 079.6 (RSV), 466.11 (acute bronchiolitis
due to RSV), and 480.1 (pneumonia due to
RSV). Age at the time of hospitalization was
determined using NHDS birth records; RSVH
rates were analyzed for infants grouped
into three age cohorts (<3 months, 3 to 6
months, and >6 to <24 months). Trends in
hospitalization rates were evaluated using
linear regression. Relative rates (RR) and 95%
confidence intervals (CI) were computed to
compare average RSVH rates for infants across
age-specific groups. The annual proportion
of RSVH by age group was also calculated.
Results: Approximately 1.1 million (90,000-
147,000 per year) RSVHs in predominantly
term children aged <24 months were analyzed.
Compared with children aged >6 to <24
months, rates for RSVH were significantly
higher among infants aged <3 months (RR,
7.38; 95% CI, 7.35-7.41) and infants aged 3
to 6 months (RR, 5.28; 95% CI, 5.26-5.29).
The proportion of RSVH in the first year of
life was lowest among infants aged <1 month
(0.9%). The greatest proportion of RSVH was
observed in children aged 3 to 6 months (14%-
23% RSVH per year; chi-square P<0.0001).
When the definition of RSVH was expanded to
include unspecified hospitalizations for acute
bronchiolitis, similar results were observed.
Conclusion: RRs were highest among the <3-
month and 3- to 6-month age groups. The
highest proportion of RSVH was among the 3-
to 6-month age group. Analysis of the impact
of RSV season, clinical practices, and other
factors on these trends is warranted.
Keywords: age; hospitalization; respiratory
syncytial virus; young infants
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2 Adv Ther (2011) 28(3)
INTRODUCTION
Respiratory syncytial virus (RSV) is recognized
as the leading cause of serious lower respiratory
tract disease in infants and young children.1-3
RSV in infants and children accounts for
approximately 50%-80% of winter bronchiolitis
and 30%-60% of winter pneumonia
hospitalizations in the United States (US).1 As
many as 125,000 infants and young children
are hospitalized in the US each year owing to
severe RSV disease, and approximately 80%
of hospitalizations involve term infants.3-5
Palivizumab was licensed in 1998 for the
prevention of RSV disease in high-risk infants.
We analyzed data from the US National
Hospital Discharge Survey (NHDS) to examine
temporal trends in RSV hospitalizations (RSVH)
among children <2 years of age. Although the
NHDS does not have information on treatment
or prophylaxis, we were interested in exploring
trends in RSVH after 1998, following the
introduction of palivizumab.
MATERIALS AND METHODS
Data from the US NHDS, a nationally
representative cohort of inpatient RSVHs in
children aged <24 months, were analyzed to
examine trends in RSVH rates by chronologic
age (CA) from 1998 (the launch of palivizumab)
to 2006. The proportion of RSVHs out of all
hospitalizations was calculated for each year
between 1998 and 2006 to examine the burden
that RSVH imposes on the US healthcare system.
Infants and children were stratified into three
mutually exclusive CA groups: <3 months, 3
to 6 months, and >6 to <24 months. Because
testing for RSV is not consistently performed in
the hospital setting, we repeated the analyses
with an expanded definition of RSV, to include
unspecified acute bronchiolitis (AB).
NHDS
Administered annually since 1965, the NHDS
is the largest available nationally representative
sur vey of inpatien t hos pitalizatio ns in
nonfederal acute care hospitals. Patient discharge
records from hospitals with 6 beds for inpatient
use were included in the survey. A three-stage
probability design based on geographic area,
hospital, and discharge data was used to select
sample data. Data were weighted to produce
national estimates. Variables collected at each
discharge included patient demographics (age,
sex, race, marital status); hospital characteristics
(geographic location, number of beds); inpatient
hospitalization characteristics (up to seven
International Classification of Diseases, 9th
Revision, Clinical Modification [ICD-9-CM]-
coded diagnoses); days of hospitalized care;
patient disposition; month, day, and year of
discharge; primary and secondary expected
source of payment; and type of admission and
procedures. Patient identifiers were removed to
ensure patient anonymity.6
Hospitalization Due to RSV
An RSVH was defined as including 1 RSV-related
ICD-9-CM code among up to seven discharge
diagnosis codes in the hospital discharge record.
For this study, RSV-related ICD-9-CM codes
included 079.6 (RSV), 466.11 (AB due to RSV), or
480.1 (pneumonia due to RSV), in the hospital
discharge records. The current study analyzed
data from 1998, as RSV codes wererst introduced
in 1996, thus allowing a 2-year period to ensure
nationwide hospital adoption of the new codes.
RSV and AB
Testing for RSV is often not consistently
performed in the hospital setting, and
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Adv Ther (2011) 28(3) 3
presumptive RSV lower respiratory infections
may frequently be coded as unspecified AB. We
therefore expanded our definition of RSVH to
include unspecified AB hospitalizations (ABH)
and conducted additional analyses based on this
expanded definition of the disease (RSVH/ABH).
Specifically, a hospital discharge with at least
one diagnosis code of 079.6 (RSV) 466.XX (AB,
unspecified), or 480.1 (pneumonia due to RSV)
was considered as RSVH/ABH.
Age
The birth month, day, and year were abstracted
from the hospital records. Age at hospitalization
was calculated by subtracting the birth date from
the hospital admission date. For purposes of
analyses, CA was categorized into three groups
(<3 months, 3 to 6 months, and >6 to <24
months). Age categories were chosen based on
the American Academy of Pediatrics guidance
for RSV prophylaxis use.7
Statistical Methods
Analyses were limited to children <24 months.
Hospital admissions related to birth were
excluded. Simple descriptive statistics were
calculated. All analyses were stratified by age
categories (<3 months, 3 to 6 months, and >6
to <24 months). All statistical analyses were
performed using Statistical Analysis Software
version 9.1 (SAS Institute Inc., Cary, NC, USA).
Incidence Calculations
Incidence rates of RSVH were calculated as the
estimated number of new RSVHs per 1000 children
for each year and age category of interest. The
number of RSVHs was determined by summing the
weighted values for each observation in the NHDS;
denominator values were estimated by the number
of live births for children using the natality data
for the corresponding year. Thus, the number of
children aged 0 to <3 months and 3 to 6 months
were each estimated by taking the annual estimate
of live births and multiplying by 0.25. The number
of children aged >6 to <24 months was estimated
by taking the annual estimate of live births and
multiplying by 1.5. Trends were calculated using
linear regression.
Relative Rates
Crude regression models were built to compare
the incidence of RSVH in older children (>6 to
<24 months of age) with younger children (<3
months, and 3 to 6 months of age). Relative rates
(RR) and associated 95% confidence intervals
(CI) were reported.
Annual Proportions
The annual proportion of hospitalizations due
to RSV was calculated to estimate the burden
that RSV imposes on the healthcare system for
the three age categories. Annual proportions of
RSVH were calculated by dividing the number
of RSVHs (as defined above) by the total
hospitalizations for that year for each of the age
categories of interest. Incidence rates, RR, and
annual proportion analyses were repeated for
RSVH/ABH as the outcome of interest.
RESULTS
Hospitalization Due to RSV
There were 1,102,293 (90,000-147,000 per
year) hospitalizations due to RSV in children
<24 months of age identified between 1998 and
2006. Most children were <3 months (40%), male
(57%), and white (61%) and lived in the southern
region of the US (37%; Table 1). Compared with
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4 Adv Ther (2011) 28(3)
children aged >6 to <24 months, rates for RSVH
were significantly higher for infants aged <3
months (RR, 7.38; 95% CI, 7.35-7.41) and infants
aged 3 to 6 months (RR, 5.28; 95% CI, 5.26-
5.29). However, the incidence of RSVH showed
a nonsignificant decrease for all age groups
from 1998 to 2006 (–0.4 per 1000 children per
year; P=0.784). Between 2000 and 2006, RSVH
decreased at a faster rate (age <3 months, –3.5 per
1000 children per year; age 3 to 6 months, –3.3
per 1000 children per year; age >6 to <24 months,
–0.35 per 1000 children per year), with the most
significant decrease (P=0.026) for children <3
months of age (Figure 1).
Between 1998 and 2006, the annual
proportion of RSVHs varied from 8% to 12% per
year for children aged <3 months, and 6% to
10% per year for children aged >6 to <24 months.
The highest proportion of hospitalizations due to
RSV (14% to 23% per year) occurred in children
aged 3 to 6 months (chi-square, P<0.0001;
Figure 2). We also examined the proportion of
hospitalizations by CA (in months) for all study
years combined (1998 to 2006) to explore the
appropriateness of the age groups analyzed (ie,
<3 months, 3 to 6 months, >6 to <24 months).
Approximately 9% of hospitalized infants aged
1 month had RSV. In contrast, approximately
20% of hospitalized infants aged 2 to 4 months
had RSV, and approximately 16% of hospitalized
children aged 5 to 8 months had RSV. After 8 and
12 months of age, the proportion of hospitalized
children with RSV fell to approximately 10%
and 7%, respectively (Figure 3).
Hospitalizations Due to RSV and AB
When the definition of RSVH was expanded
to include unspecified ABH, the total number
of hospitalizations for children aged <24
months between 1998 and 2006 increased to
1,928,520. Results for RR, annual incidences,
and annual proportions by CA were similar
for RSVH and RSVH/ABH. Rates for RSVH/
Characteristic RSV hospitalizations, n (%)
Age, months
<3
3 to 6
>6 to <24
436,921 (40)
312,088 (28)
353,284 (32)
Sex
Male
Female
629,361 (57)
472,932 (43)
Race
White
Black
Other
677,510 (61)
142,690 (13)
282,093 (26)
Region
Northeast
Midwest
South
West
139,024 (13)
227,465 (21)
408,907 (37)
326,897 (30)
Table 1. Characteristics of children aged <24 months with RSV hospitalizations* from 1998 to 2006.
RSV= respiratory syncytial virus. *Newborn hospitalizations were excluded.
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Adv Ther (2011) 28(3) 5
Figure 1. RSV hospitalization rates by age group for children <24 months: 1998-2006. RSV=respiratory syncytial virus.
0
70
60
50
40
30
20
10
RSV hospitalizations per 1000 children
Year
1998 1999 2000 2001 2002 2003 2004 20062005
<3 months 3 to 6 months >6 to <24 months
Figure 2. Proportion of RSV hospitalizations among all hospitalizations stratied by age group: 1998-2006.
RSV=respiratory syncytial virus.
0.00
0.25
0.20
0.15
0.10
0.05
Proportion of RSV hospitalizations
Year
1998 1999 2000 2001 2002 2003 2004 20062005
<3 months 3 to 6 months >6 to <24 months
Figure 3. Proportion of RSV hospitalizations by chronologic age: 1998-2006. RSV=respiratory syncytial virus.
0.00
0.25
0.20
0.15
0.10
0.05
Proportion of RSV hospitalizations
Chronologic age (months)
1 2 3 4 5 6 7 8 9 10 11 12 to <24
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6 Adv Ther (2011) 28(3)
ABH were significantly higher for infants
aged <3 months (RR, 5.45; 95% CI, 5.43-
5.47) and infants aged 3 to 6 months of age
(RR, 5.11; 95% CI, 5.10-5.13), compared with
children aged >6 to <24 months. As with
RSVH, RSVH/ABH rates declined faster after
the year 2000 for children aged <3 months
(−5.3 per 1000 children per year; P=0.008)
and children aged 3 to 6 months (−7.0 per
1000 children per year; P=0.028) compared
with children aged >6 to <24 months (0.03
per 1000 children per year; P=0.446); the
percentage of RSVHs/ABHs was greatest for
those aged 3 to 6 months (30% to 40% of
total annual hospitalizations, compared with
14% to 20% of annual hospitalizations in the
other two age categories), and for those with
a CA of 2 to 8 months (27% to 37% of total
annual hospitalizations; data not shown).
DISCUSSION
RSV lower respiratory tract infection remains
the most important cause of rehospitalization
in infants and young children.1,5 Consistent
with results from other studies,1-5 we found that
RR of RSVH were significantly higher (P<0.001)
in children 6 months of age compared
with children with a CA of >6 months. The
incidence of RSVH appeared to decrease in a
nonsignificant fashion among children of all
ages from 1998 to 2006. The only significant
decrease in hospitalization rates was observed
in infants with a CA of <3 months (P=0.026).
This may reflect greater protection due to the
implementation of the 3-month maternity leave
and increased awareness of the importance of
protection from RSV in this very young age
group. The overall decreasing trend for RSVH in
all infants and children may also be a reflection
of the shift towards outpatient management of
RSV disease.4
This study also assessed annual proportions
by month of CA as an estimate of the burden
imposed by RSVH. The proportion of RSVH in the
first year of life was lowest in infants with a CA
of <1 month (0.9%). We speculate that this may
be due to a combination of diminished exposure
to RSV, and high maternal antibody levels.8,9 The
largest proportion of RSVH occurred in children
with a CA of 2 to 4 months (20%) and 5 to 8
months (16%). Additional RSVH risk factors
in these groups may include immunologic
vulnerability to severe RSV illness due to the
nadir in circulating maternal immunoglobulin
G antibody9 and increased RSV exposure of
older infants in situations such as day care.8 The
proportion of RSVH remained high for children
through the first year of life: 13% at a CA of 8
months, and 10% at 11 months.
It has been reported that RSV testing is not
performed in up to 30% of suspected cases.4 We
therefore expanded our definition of RSVH to
include unspecified AB and reanalyzed the data
using the expanded definition of the disease. For
all analyses, results were similar. We found no
evidence that potential misclassification of RSV
or frequency of RSV testing played an important
role in the trends we observed.
The strengths of this study include its large
sample size, records-based data collection,
broad geographic scope, and prolonged period
of surveillance (eight RSV seasons). However, a
number of study limitations exist. RSV testing
was not routinely employed. Furthermore, we
could not validate the type of RSV test used
for those who were tested. This study was also
historical in nature, and the hospital discharge
data used could have included coding errors.
We believe that the findings from this study
are an important step in the further delineation
of those infants and children at highest risk for
RSVH. Further studies are warranted, as such
information could have important implications
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Adv Ther (2011) 28(3) 7
for future development of guidelines for RSV
immunoprophylaxis and vaccines.
ACKNOWLEDGMENTS
This research was sponsored by MedImmune,
LLC, Gaithersburg, MD, USA. Editorial assistance
in formatting the manuscript for submission
was provided by Complete Healthcare
Communications, Inc. (Chadds Ford, PA), and
funded by MedImmune.
Financial disclosures: Drs. Fryzek, Martone,
and Groothius are employees of MedImmune.
Presentation at Scientific Conferences: portions
of this manuscript have been presented at the
following conferences: Pediatric Academic
Societies’ Annual Meeting, May 1-4, 2010,
Vancouver, BC, Canada; The 3rd Congress of
the European Academy of Paediatric Societies,
October 23-26, 2010, Copenhagen, Denmark;
American Academy of Pediatrics National
Conference & Exhibition, October 2-5, 2010,
San Francisco, CA.
Jessie R. Groothuis is the guarantor for this
article, and takes responsibility for the integrity
of the work as a whole.
Open Access. This article is distributed
under the terms of the Creative Commons
Attribution Noncommercial licence which
permits any noncommercial use, distribution,
and reproduction in any medium, provided the
original author(s) and source are credited.
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... [1][2][3][4][5][6] More than 100 000 children are hospitalized for RSV per year, making RSV the most common diagnosis for hospitalized infants. [6][7][8] RSV infection can be particularly severe in children ,1 year of age and infants with congenital heart disease, prematurity, and chronic lung disease. 9,10 The Centers for Disease Control and Prevention (CDC) defines the start of RSV regional activity season as $10% positive RSV testing for 2 consecutive weeks. ...
... However, in 2 regions (3 and 10), the first palivizumab dose was given at the start of or after hospitalization season onset during at least 1 season. In addition, the first palivizumab dose was given more than 12 weeks before the start of RSV hospitalization season onset in 4 regions (5,(8)(9)(10) for at least 1 season. The last inpatient dose of palivizumab in a region was given at a mean of 0.7 (SD 3.6) weeks before RSV hospitalization season offset and 3.7 (SD 3.4) weeks after regional activity offset. ...
... RSV activity can differ within regions and from year to year. 1,8,10,27 Furthermore, different areas within the same state can have vastly different patterns of RSV activity; for example, regional RSV activity season can last between 7 and 11 months long, depending on the region, in Florida. 22 Using regional activity data from individual cities instead of set calendar dates can increase the proportion of patients appropriately receiving palivizumab before RSV becoming prevalent in an area. ...
Article
Objectives: To compare pediatric respiratory syncytial virus (RSV) hospitalizations in the United States to regional RSV activity and inpatient palivizumab administration. Methods: We characterized inpatients, excluding newborns, with RSV from the Pediatric Health Information System (July 2010-June 2013). RSV regional activity timing was defined by the National Respiratory and Enteric Virus Surveillance System. RSV hospitalization season (defined by at least 3 SDs more than the mean regional baseline number of RSV hospitalizations for 3 consecutive weeks) was compared with RSV regional activity season (2 consecutive weeks with ≥10% RSV-positive testing). Logistic regression was used to determine predictors of hospitalization timing (ie, during or outside of regional activity season). We also assessed the timing of inpatient palivizumab administration. Results: There were 50 157 RSV hospitalizations. Mean RSV hospitalization season onset (early November) was 3.3 (SD 2.1) weeks before regional activity season onset (early December). Hospitalization season offset (early May) was 4.4 (SD 2.4) weeks after activity season offset (mid-April). RSV hospitalization and activity seasons lasted 18 to 32 and 13 to 23 weeks, respectively. Nearly 10% of hospitalizations occurred outside of regional activity season (regional ranges: 5.6%-22.4%). Children with chronic conditions were more likely to be hospitalized after regional activity season, whereas African American children were more likely to be hospitalized before. Inpatient palivizumab dosing was typically initiated before the start of RSV hospitalizations. Conclusions: There is regional variation in RSV hospitalization and activity patterns. Many RSV hospitalizations occur before regional activity season; high-risk infants may require RSV immunoprophylaxis sooner.
... The Global Burden of Disease study estimated that RSV accounted for 1.6% of deaths worldwide in 2010 [95]. Presence of older sibling [2,108] Birth in proximity to RSV season [16,109,110] Low birth weight [108,110] Birth order [33,109] Male sex [108] Young age (\6 months) [14,16,27,100] Exposure to smoking [86,101,108] Maternal age [110] Suburban residence [110] Other risk factors associated with RSV hospitalization Vitamin D deficiency [111] Family history of atopy/atopic diagnosis [101,112,113] Climatic factors and air pollution [114][115][116] High altitude above 2500 m [104] Socioeconomic status/parental education [117] Delivery by cesarean section [105] Level of evidence a ...
... Several important independent risk factors for RSV hospitalization have been identified, including male gender, birth in proximity to RSV season, history of prematurity and tobacco smoke exposure (Table 4). Age, in particular, has been found to be a significant predictor in the severity of infection and RSV hospitalization, with the youngest age groups (\6 months) more frequently hospitalized for a RSV infection [14,16,27,100,101]. In contrast, some risk factors, such as breastfeeding, have been found to be protective [33,102]. ...
Article
Full-text available
Background Moderate-late preterm infants, 33–35 weeks’ gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants. Methods A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants’ 33⁰–35⁶ wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed. Results The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days. Conclusions The burden of RSVH in moderate-late, 33–35 weeks’ wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy.
... The Global Burden of Disease study estimated that RSV accounted for 1.6% of deaths worldwide in 2010 [95]. Presence of older sibling [2,108] Birth in proximity to RSV season [16,109,110] Low birth weight [108,110] Birth order [33,109] Male sex [108] Young age (\6 months) [14,16,27,100] Exposure to smoking [86,101,108] Maternal age [110] Suburban residence [110] Other risk factors associated with RSV hospitalization Vitamin D deficiency [111] Family history of atopy/atopic diagnosis [101,112,113] Climatic factors and air pollution [114][115][116] High altitude above 2500 m [104] Socioeconomic status/parental education [117] Delivery by cesarean section [105] Level of evidence a ...
... Several important independent risk factors for RSV hospitalization have been identified, including male gender, birth in proximity to RSV season, history of prematurity and tobacco smoke exposure (Table 4). Age, in particular, has been found to be a significant predictor in the severity of infection and RSV hospitalization, with the youngest age groups (\6 months) more frequently hospitalized for a RSV infection [14,16,27,100,101]. In contrast, some risk factors, such as breastfeeding, have been found to be protective [33,102]. ...
Article
Full-text available
Introduction: The REGAL (RSV [respiratory syncytial virus] Evidence-a Geographical Archive of the Literature) series provides a comprehensive review of the published evidence in the field of RSV in Western countries over the last 20 years. This first of seven publications covers the epidemiology and burden of RSV infection. Methods: A systematic review was undertaken for articles published between Jan 1, 1995 and Dec 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov. Studies reporting data for hospital visits/admissions for RSV infection among children (≤18 years of age), as well as studies reporting RSV-associated morbidity, mortality, and risk factors were included. Study quality and strength of evidence (SOE) were graded using recognized criteria. Result: 2315 studies were identified of which 98 were included. RSV was associated with 12-63% of all acute respiratory infections (ARIs) and 19-81% of all viral ARIs causing hospitalizations in children (high SOE). Annual RSV hospitalization (RSVH) rates increased with decreasing age and varied by a factor of 2-3 across seasons (high SOE). Studies were conflicting on whether the incidence of RSVH has increased, decreased, or remained stable over the last 20 years (moderate SOE). Length of hospital stay ranged from 2 to 11 days, with 2-12% of cases requiring intensive care unit admission (moderate SOE). Case-fatality rates were <0.5% (moderate SOE). Risk factors associated with RSVH included: male sex; age <6 months; birth during the first half of the RSV season; crowding/siblings; and day-care exposure (high SOE). Conclusion: RSV infection remains a major burden on Western healthcare systems and has been associated with significant morbidity. Further studies focusing on the epidemiology of RSV infection (particularly in the outpatient setting), the impact of co-infection, better estimates of case-fatality rates and associated risk factors (all currently moderate/low SOE) are needed to determine the true burden of disease. Funding: Abbvie.
... Studies were conducted in various states and regions (Supplementary Table 2). Thirteen [2,4,7,[13][14][15][16][17][18][19][20][21][22] used nationally representative databases, including National (Nationwide) Inpatient Sample, Kids' Inpatient Database, National Hospital Discharge Survey, and National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey. Three [5,23,24] were based on the New Vaccine Surveillance Network comprising IPs, EDs, and OP clinics located in 3-7 states. ...
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Background: The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized. Methods: We systematically reviewed studies of RSV and bronchiolitis published 2000-2021 (data years, 1979-2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools. Results: We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6-11 months in 2006 to 50.1 per 1000 per year among infants aged 0-2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0-22.7 per 1000 in 1997-1999 and 1997-2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non-high-risk infants in 1997-2012. Conclusions: Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.
... This finding is in agreement with the results of previous studies that reported that younger age is associated with a higher risk of severe RSV-associated disease and hospitalizations. 3,8,[31][32][33] Moreover, compared with RSV-negative children, RSV-positive children were more likely to have a higher respiratory rate, retraction, flaring, grunting, and wheezing, which are indicative of a more severe presentation. ...
Article
Acute lower respiratory infection (ALRI) is a major cause of morbidity and mortality worldwide. Data regarding the etiology of acute respiratory infection (ARI) is scarce in developing countries. The aim of this study was to identify the viral etiology of ARI/ALRI in hospitalized children and factors associated with increased length of stay (LoS) and severe disease presentation in Northern Jordan. This was a prospective viral surveillance study using real-time reverse transcriptase-polymerase chain reaction in children younger than 5 years admitted with ARI to two main hospitals in Northern Jordan during the winter of 2016. Nasopharyngeal swabs were obtained and tested for respiratory syncytial virus (RSV) and other viruses. Demographic and clinical characteristics of RSV-positive patients were compared with those of RSV-negative patients. There were 479 patients hospitalized with ARI. Their mean age (standard deviation) was 10.4 (11.6) months. 53.9% tested positive for at least one virus, with RSV being the most commonly detected virus (34%). Compared with RSV-negative patients, RSV-positive patients were younger, more likely to have chronic lung disease, and more likely to present with cough, rhinorrhea, difficulty in breathing, retraction, flaring, grunting, wheezing, and a higher respiratory rate. Prematurity, presence of a chronic illness, oxygen saturation < 90%, and atelectasis and consolidation on chest X-rays were significantly associated with an increased mean LoS. Patients with a history of prematurity had higher risk of severe disease (odds ratio = 2.6; 95% confidence interval: 1.5, 4.7; p = 0.001). Compared with patients 6 months old and younger, patients aged 6.1 to 12 months were less likely to have severe disease. Human metapneumovirus (HMPV)-positive ALRI was associated with increased odds of severe disease. Viruses are recognized as etiological agent of ARI/ALRI-associated morbidity in developing countries that need more attention and implementation of targeted strategies for prevention and detection. HMPV can be a cause of severe ALRI.
... We found the highest rate of RSV among infants aged 3-5 months with RSV detection in nearly three over four patients (73.5%) followed by infants < 3 months (53.7%). Similar to our results, other reports found that infants aged 3-5 months had the highest proportion of RSV detection [3,10], while the highest RSV frequency in the South African study was among infants < 3 months [9]. ...
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Purpose To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. Methods Data from a prospective study conducted during the peak of five influenza seasons in the Province of Quebec, Canada were used. Results We detected higher frequency of RSV compared to influenza viruses (55.3% vs. 16.3%). Radiologically confirmed pneumonia was significantly more frequent in children with RSV (39%) than those with influenza (18%) and the clinical course was more severe in RSV than influenza-infected children, especially among infants < 3 months. Conclusion Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months.
... Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants worldwide each year. In the United States, more than 100,000 children under 1 year of age are admitted annually to the hospital because of severe consequences of RSV infection, making RSV the most common primary diagnosis for hospitalized infants (1)(2)(3). In the United States, RSV hospitalizations are seasonal and may vary substantially, depending on the region (4). ...
Article
Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants worldwide each year. Both host and viral factors host factors predispose a subset of what appear to be healthy infants to severe RSV-induced disease. In this review, we outline many genetic and immunologic factors that contribute to airway obstruction that contributes to the severity of RSV infection.
... Estudo realizado na Espanha avaliou 229 pacientes internados em UTI pediátrica por BVA e constatou que a idade foi inversamente proporcional ao tempo necessário de suporte ventilatório e de dias de internação em UTI 18,19,20 . Um estudo realizado nos Estados Unidos apontou que de 1,1 milhão de crianças menores de dois anos internadas por VSR em um período de oito anos, a maior porcentagem das internações ocorreu na faixa etária entre três e seis meses 21 . ...
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Objetivo: Avaliar a utilização da ventilação mecânica não invasiva (VMNI) sobre parâmetros clínicos nas primeiras 24 horas em pacientes internados em uma emergência pediátrica com diagnóstico de bronquiolite viral aguda (BVA).Materiais e Métodos: Estudo de coorte retrospectivo através de coleta de dados de prontuários de crianças internadas com diagnóstico de BVA que fizeram uso de VMNI em uma emergência pediátrica durante dois invernos consecutivos. Dados coletados: demográficos (sexo, idade), características clínicas (frequência cardíaca, frequência respiratória, saturação periférica de oxigênio), tempo de uso da VMNI, internação em UTI pediátrica e tempo de internação. Foram utilizados testes de Friedman e Wilcoxon para comparação de variáveis clínicas entre cada período de tempo, teste de Mann-Withney e ANOVA para comparações entre o grupo que utilizou e não utilizou VMNI.Resultados: Amostra composta por 14 pacientes, o tipo de vírus mais prevalente foi o vírus sincicial respiratório, o modo ventilatório não invasivo predominantemente utilizado foi o CPAP. Não houve diferença significativa dos sinais vitais em relação ao momento da instalação da VMNI, seis, 12 e 24 horas. Na utilização de oxigênio suplementar houve diferença significativa entre o momento da instalação da VMNI e após 24 horas. Quando comparadas as características clínicas dos pacientes que falharam na VMNI e necessitaram de suporte ventilatório invasivo, a frequência cardíaca diferiu significativamente tanto no momento da instalação da VMNI como após 6 horas.Conclusão: Houve redução significativa da necessidade de oxigênio suplementar após 24 horas da instalação da VMNI. Não foram observadas diferenças significativas nas demais características clínicas dos pacientes.
... Dougherty and Meissner [24], using data from 1994 to 1997 from a pediatric hospital, Table 3 continued Fryzek et al. [26] did not present RSV hospitalizations by each month of chronologic age, but RSV hospitalizations were reported to be greatest among infants aged \3 months. A prospective study by Ambrose and coauthors observed that the risk of RSV hospitalization for infants 32-35 wGA was highest for infants in the first 6 months of life [4]. ...
Article
Introduction: Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States, and the risk for RSV hospitalizations is greater for infants born preterm. Recent studies in preterm and term infants have shown that RSV hospitalization rates vary considerably depending on infant chronologic age. This study sought to aggregate the data available from published literature and from nationally representative databases of US infant hospitalizations to generate a composite description of the effect of young chronologic age on RSV hospitalizations among US preterm and term infants by individual month of age. Methods: Data describing the relative incidence of RSV hospitalizations by individual month of chronologic age during the first year of life were obtained from recently published studies, the 2006-2011 National Inpatient Sample databases, and the 2006 and 2009 Kids Inpatient Databases. Results: All data sources showed that ≥20% of infant RSV hospitalizations occurred in the second month of life and >50% and >75% of RSV hospitalizations were observed during the first 3 and 6 months of life, respectively. These findings were consistent for both preterm and term infants. Conclusion: Data from multiple sources demonstrate that the greatest risk of RSV hospitalization occurs during the first 6 months of life among US preterm and term infants. Strategies to prevent infant RSV hospitalizations should be targeted to infants during the first months of life. Funding: AstraZeneca.
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Respiratory syncytial virus (RSV) causes more lower respiratory tract infections, often manifested as bronchiolitis, among young children than any other pathogen. Few national estimates exist of the hospitalizations attributable to RSV, and recent advances in prophylaxis warrant an update of these estimates. To describe rates of bronchiolitis-associated hospitalizations and to estimate current hospitalizations associated with RSV infection. Descriptive analysis of US National Hospital Discharge Survey data from 1980 through 1996. Children younger than 5 years who were hospitalized in short-stay, non-federal hospitals for bronchiolitis. Bronchiolitis-associated hospitalization rates by age and year. During the 17-year study period, an estimated 1.65 million hospitalizations for bronchiolitis occurred among children younger than 5 years, accounting for 7.0 million inpatient days. Fifty-seven percent of these hospitalizations occurred among children younger than 6 months and 81 % among those younger than 1 year. Among children younger than 1 year, annual bronchiolitis hospitalization rates increased 2.4-fold, from 12.9 per 1000 in 1980 to 31.2 per 1000 in 1996. During 1988-1996, infant hospitalization rates for bronchiolitis increased significantly (P for trend <.001), while hospitalization rates for lower respiratory tract diseases excluding bronchiolitis did not vary significantly (P for trend = .20). The proportion of hospitalizations for lower respiratory tract illnesses among children younger than 1 year associated with bronchiolitis increased from 22.2% in 1980 to 47.4% in 1996; among total hospitalizations, this proportion increased from 5.4% to 16.4%. Averaging bronchiolitis hospitalizations during 1994-1996 and assuming that RSV was the etiologic agent in 50% to 80% of November through April hospitalizations, an estimated 51, 240 to 81, 985 annual bronchiolitis hospitalizations among children younger than 1 year were related to RSV infection. During 1980-1996, rates of hospitalization of infants with bronchiolitis increased substantially, as did the proportion of total and lower respiratory tract hospitalizations associated with bronchiolitis. Annual bronchiolitis hospitalizations associated with RSV infection among infants may be greater than previous estimates for RSV bronchiolitis and pneumonia hospitalizations combined.
Article
Objectives: To provide current estimates of the incidence, associated risk factors, and costs of severe respiratory syncytial virus (RSV) infections among infants in the United States, denned as emergency department (ED) visits, hospitalization, and death. Study design: Retrospective analysis of National Hospital Ambulatory Medical Care Survey data 1997 to 2000; National Hospital Discharge Survey data 1997 to 2000; Perinatal Mortality Linked Files 1998 to 1999. The Hospital Cost Utilization Inpatient Sample data 1997 to 2000 were used to estimate hospitalization costs, and the 2001 Medicare fee schedule was used to estimate ED visit costs. Census data were used for population estimates. Between 1997 and 2000, there were 718,008 ED visits by infants with lower respiratory infection diagnoses during the RSV season (22.8/1000), and 29% were admitted. Costs of ED visits were approximately $202 million. RSV bronchiolitis was the leading cause of infant hospitalization annually. Total hospital charges for RSV-coded primary diagnoses during the 4 years were more than $2.6 billion. An estimated 390 RSV-associated postneonatal deaths occurred in 1999. Low birth weight and prematurity significantly increased RSV-associated mortality rates. Conclusions: RSV is a major cause of infant morbidity and mortality. Severe RSV is highest among infants of black mothers and Medicaid-insured infants. Prematurity and low birth weight significantly increase RSV mortality rates.
Article
Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous ( RSV- IGIV) are licensed by the Food and Drug Administration for use in preventing severe lower respiratory tract infections caused by respiratory syncytial virus ( RSV) in high- risk infants, children younger than 24 months with chronic lung disease ( formerly called bronchopulmonary dysplasia), and certain preterm infants. This statement provides revised recommendations for administering RSV prophylaxis to infants and children with congenital heart disease, for identifying infants with a history of preterm birth and chronic lung disease who are most likely to benefit from immunoprophylaxis, and for reducing the risk of RSV exposure and infection in high- risk children. On the basis of results of a recently completed clinical trial, prophylaxis with palivizumab is appropriate for infants and young children with hemodynamically significant congenital heart disease. RSV- IGIV should not be used in children with hemodynamically significant heart disease. Palivizumab is preferred for most high-risk infants and children because of ease of intramuscular administration. Monthly administration of palivizumab during the RSV season results in a 45% to 55% decrease in the rate of hospitalization attributable to RSV. Because of the large number of infants born after 32 to 35 weeks' gestation and because of the high cost, immunoprophylaxis should be considered for this category of preterm infants only if 2 or more risk factors are present. High- risk infants should not attend child care during the RSV season when feasible, and exposure to tobacco smoke should be eliminated.
Article
2 S.D. log-normal ranges of serum-γG-globulin levels have been established for 182 babies of normal weight for gestational ages from twenty-four to forty weeks. 34 babies of multiple pregnancy had normal γG levels for their gestation. 28 "small-for-dates" and 12 post-mature babies had significantly lower γG levels, which may account for some of their increased death-rate, a major cause of which is pneumonia. The finding of a low serum-γG-globulin
Article
The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection.
Article
The relation of breast feeding and other factors to the incidence of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRI) in the first year of life is examined. The study population is 1,179 healthy infants enrolled at birth between May 1980 and January 1984 into the Tucson Children's Respiratory Study, Tucson, Arizona. Each subject's data were assessed at each month of age during the first year of life, during those months when respiratory syncytial virus was isolated. A number of significant relations were observed, particularly between 1 and 3 months of age. At this age, the risk of having a RSV-LRI increased in association with less than 1-month or no breast feeding, with being male, and with increasing numbers of others sharing the child's bedroom. In multivariate analysis, only sex and the number of others sharing the room remained as significant direct effects. However, a significant interaction demonstrated that breast feeding has a protective role in relation to RSV-LRIs for those infants of mothers with a lower education level. The risk of having a RSV-LRI increases with combinations of risk factors. Being in day care was a significant risk factor in the 7- to 9-month age range. The RSV-LRI rate also varies by birth month. A separate case-control study assessed relations of RSV-LRIs with cord serum RSV antibody. Those with lower cord serum RSV antibody, who also have minimal breast feeding, were found to be especially at risk for RSV-LRIs in the first 5 months of life.
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We describe respiratory syncytial virus (RSV)-specific cytotoxic T-cell (CTL) lines and clones developed from the spleens of C57BL/6 and BALB/c mice. Line 7 and clones derived from it were H-2Kb restricted, whereas line 12 had both Kb and Db components. Both lines, and all the clones except one, could lyse targets infected with either strain A or strain B RSV. Line 7 or 7-11E1 cells (8 x 10(6) to 10 x 10(6) given intravenously cleared RSV from the lungs of infected mice. There was no morbidity or mortality in any of the infected mice whether or not they received T cells. The C57BL/6 mouse is a useful model system in which to study the role of the CTL response in protective immunity to RSV. CTL lines and clones can mediate clearance of RSV from the lungs of normal mice without producing any associated morbidity.
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Twenty-five years ago an agent recovered from chimpanzees suffering from a cold was entitled 'CCA'-chimpanzee coryza agent. Over the ensuing years, the agent, more appropriately renamed respiratory syncytial virus (RSV), has come to be recognized as the most important cause of lower respiratory tract disease in infants and young children.
The National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges from non-Federal hospitals, began in 1965 and has been conducted annually since then. The original design of NHDS was in place through 1987. This report provides information about the survey design, instruments, data collection procedures, and survey methodology used for NHDS since the implementation of its redesign in 1988.