PEER-REVIEWED ARTICLE
Epidemiology of Respiratory Syncytial Virus in
Various Regions Within North Carolina During
Multiple Seasons
David A. Wilfret, MD; Brent T. Baker, MD; Elizabeth Palavecino, MD; Cassandra Moran, DO;
Daniel K. Benjamin Jr., MD, PhD
Abstract
Background: The Centers for Disease Control and Prevention (CDC) monitors the occurrence of respiratory syncytial virus (RSV) in the
United States and has historically reported on activity at the regional level. Prior to the 2007-2008 RSV season, the CDC did not report seasonal
RSV data for cities within North Carolina or for the state. The purpose of the present study is to characterize RSV seasonal activity within North
Carolina and to determine the appropriate months in which at-risk children should receive prophylaxis.
Methods: We prospectively collected RSV test data monthly over three seasons (fall through spring), from September 2003 through July 2006,
from a diverse group of hospitals and a community pediatric practice located within five regions throughout North Carolina.
Results: Approximately 14,000 laboratory tests, including 23.7% that were RSV positive, were evaluated over the three seasons, and RSV was
detected within the state during all but three months of the study. Seasonal variation in the onset (October-November) of RSV activity and duration
(six to seven months) of the RSV season according to the specified definition of seasonality was noted yearly within individual regions and among
regions. On average over the study period, the greatest percentage of positive tests (33.8%) statewide occurred during January.
Conclusions: Our data suggest the RSV season in North Carolina is longer than the national average, and RSV epidemics persist during
months that fall outside of those in which RSV prophylaxis is given to high-risk children. Guidelines on the administration of RSV prophylaxis should
ideally be based on results of local RSV test data.
Keywords: respiratory syncytial virus (RSV); surveillance; seasonality; palivizumab; North Carolina
R
espiratory syncytial virus (RSV) is a major cause of lower
respiratory tract infections among young children1 and is
responsible for more hospitalizations—approximately 2.4 per
100 births yearly—than any other disease during infancy.2,3
RSV affects nearly all children at least once by age 2.4 Those
born prematurely or with either a history of chronic lung disease
or significant congenital heart disease are at highest risk for
severe disease.5 Potential consequences of RSV-related infection
include recurrent wheezing and asthma through later life6 and
deaths.7 This underscores the need for adequate preventive
measures. There are no vaccines currently available against RSV,
but the severity of infection and likelihood for hospitalization
are reduced in at-risk children who are administered palivizumab
prior to and during the RSV season.5,8,9
Recommendations on the use of palivizumab are issued
periodically by the Committee on Infectious Diseases and
published in the Redbook.5 The most current guideline states
that palivizumab should be administered as a series of five
monthly injections beginning in November and ending in
March. However, these recommendations do not take into
consideration the substantial seasonal variability in the onset
and duration of RSV epidemics noted over time within a given
geographic area or among different regions of the country.10
The Centers for Disease Control and Prevention (CDC) has
monitored temporal and geographic trends for RSV activity
through a passive surveillance system (i.e., National Respiratory
and Enteric Virus Surveillance System [NREVSS]) that
includes approximately 70 laboratories located throughout the
David A. Wilfret, MD, is a research fellow in the Department of Pediatrics at Duke University Medical Center.
Brent T. Baker, MD, is a pediatrician for the North Carolina Respiratory Syncytial Virus Study Team.
Elizabeth Palavecino, MD, is a medical microbiologist for the North Carolina Respiratory Syncytial Virus Study Team.
Cassandra Moran, DO, is an instructor in the Department of Pediatrics at Duke University Medical Center.
Daniel K. Benjamin Jr., MD, PhD, is an associate professor in the Department of Pediatrics at Duke University Medical Center. He can
be reached at danny.benjamin (at) duke.edu.
NC Med J November/December 2008, Volume 69, Number 6
447
country. Results of RSV test data from participating sites for
the 2003 through 2006 RSV seasons were grouped into one of
four regions, and seasonal data were reported by region and not
state, with the exception of Florida.11 There has been increased
interest by individual state departments of health12,13 and
independent investigators14-17 to gain a better understanding of
the seasonality of RSV at the local level and to place less
reliance on regional data. As a result, more than 20 state health
departments have some form of RSV surveillance program.
Recognizing the need for better reporting of local data, the
number of reporting laboratories within the NREVSS has been
greatly expanded and state data are currently available (i.e., as
of the 2007-2008 RSV season) through the network. At the
time of our study, North Carolina did not have any formal
coordinated RSV monitoring program, and to our knowledge
there were no available published data on the seasonality of
RSV within the state. The purpose of this study was to identify
when RSV was present in epidemic levels within different
regions of the state over time and to determine the appropriate
timing and duration of RSV prophylaxis specific to North
Carolina.
METHODS
We prospectively collected RSV test data monthly from
children over three seasons (fall through spring), beginning
September 2003 and ending July 2006 from a diverse group of
academic and community hospitals and a group of pediatric
primary care offices. The purpose of the study was to determine
the onset, peak, duration, and conclusion of each RSV season
within various regions of the state and in the state overall. A
further objective was to determine appropriate timing and
duration of palivizumab prophylaxis specific for North Carolina.
Laboratory tests from patients were reported monthly and
the number of positive tests was divided by the total number of
tests to determine the percent of positive tests by region and for
the state. The onset of the RSV season was defined as the first
of consecutive months in which 10% or more of RSV tests
were positive and at least 10 tests were reported. If fewer than
10 tests were reported, RSV was considered not to be present
during the month. The conclusion of the RSV season was
defined as the first month following successive epidemic months
in which <10% of tests were positive or fewer than 10 tests were
noted. To simulate real-life conditions, each site used its own
collection and testing methods and made its own determination
as to which patients would be tested. Presence of RSV was
confirmed through antigen detection methods such as virus
direct fluorescent assay (VDFA) and enzyme immunoassay (EIA)
and/or viral culture. Antigen detection assays, rather than viral
cultures, were used to determine the RSV season, as viral culture
results were only available from one site. Data were submitted
and analyzed at the Duke Clinical Research Institute.
The participating institutions included academic and
community hospitals and a group of pediatric primary care
offices, which represented five regions within the state. Sites
included Wake Medical Center (now known as WakeMed) in
448
Raleigh (north central North Carolina); four sites in
Greensboro/Winston-Salem (northwestern North Carolina),
which included Baptist Medical Center, Forsyth Medical
Center, High Point Regional Hospital, and Moses H. Cone
Memorial Hospital; Pitt County Memorial Hospital in
Greenville (eastern North Carolina); Carolinas Medical Center
in Charlotte (southwestern North Carolina); and three sites of
Hendersonville Pediatrics located in Brevard, Fletcher, and
Hendersonville (western North Carolina). The populations of
the study areas are quite variable, representing urban (200,000650,000 people; Winston-Salem, Greensboro, Raleigh, Charlotte),
suburban (72,000 people; Greenville), and rural locales (5,00015,000 people; Fletcher, Brevard, Hendersonville). The farthest
distance spanning any two sites exceeds 300 miles, between
Brevard and Greenville; the closest distance, between Baptist
Medical Center and Forsyth Medical Center, is approximately
three miles.
Data from Forsyth Medical Center, High Point Regional
Hospital, Moses H. Cone Memorial Hospital, and Baptist
Medical Center were pooled as one regional site (Greensboro/
Winston-Salem), as were data from all sites of Hendersonville
Pediatrics. Wake Medical Center and the four sites in
Greensboro/Winston-Salem reported data throughout each of
the three study seasons: 2003-2004, 2004-2005, and 2005-2006.
Pitt County Memorial Hospital collected data through two
seasons (2003-2004 and 2004-2005), whereas Carolinas
Medical Center and Hendersonville Pediatrics reported data for
a lone season each (2003-2004 and 2005-2006, respectively).
RESULTS
Approximately 14,000 RSV test results were reported during
the evaluation period and almost 80% of all data were
contributed from the Greensboro/Winston-Salem and Wake
Medical Center sites. All patients were children, but further
demographic data (i.e., ages, gender, race) were not available.
Seasonal variation in the onset of RSV activity, month of peak
activity, and duration of the RSV season was noted yearly within
individual regions and among regions. Collectively, RSV was
detected during all but three months, seasons began in the
months of October or November, activity peaked between
November and February (most often January), and seasons
concluded in March, April, or May. Seasons lasted from two to
seven months in individual regions and six months statewide
during the 2003-2004 and 2004-2005 seasons and seven
months statewide during the 2005-2006 season.
Statewide Results
During the three seasons, 13,920 samples were collected
overall from five regions across the state, and of these, 3,297
(23.7%) were positive (see Table 1). The month with the most
laboratory test reports was December (3,501) although the
greatest percentage of positive tests (33.8%) occurred during
January. The highest percentage of positive RSV tests occurred
during the 2005-2006 season (29.2%), with data for the other
two seasons being fairly similar around 21% to 22%.
NC Med J November/December 2008, Volume 69, Number 6
Table 1.
Percent Positive RSV Tests From All Sites During Each RSV Season
Month
2003-2004
2004-2005
2005-2006
Total
7.2
a
(9/125)
1.9
(2/104)
3.4
(2/58)
4.5
(13/287)
October
17.7
(72/407)b
6.1
(16/263)
9.6
(22/228)
12.2
(110/898)
November
26.3
(187/712)
15.4
(68/441)
27.2
(115/423)
23.5
(370/1576)
December
17.7
(304/1722)
32.8
(248/757)
40.8
(417/1022)
27.7
(969/3501)
January
29.9
(272/910)
34.3
(309/902)
36.9
(384/1042)
33.8
(965/2854)
February
31.7
(214/675)
20.9
(147/703)
26.6
(174/654)
26.3
(535/2032)
March
14.6
(88/603)
11.4
(58/507)
20.0
(90/449)
15.1
(236/1559)
April
4.3
(12/281)
10.5
(18/171)
15.0
(30/200)
9.2
(60/652)
May
5.3
(5/95)
6.6
(8/122)
11.9
(13/109)
8.0
(26/326)
June
0.0
(0/37)
0.0
(0/9)
5.3
(3/57)
2.9
(3/103)
July
10.0
(2/20)
7.1
(1/14)
10.5
(6/57)
9.9
(9/91)
0.0
(0/32)
(1/9)c
–
2.4
(1/41)
20.7
(1165/5619)
September
August
Total
11
21.9
(876/4002)
–
29.2 (1256/4299)
23.7 (3297/13920)
a Numbers in parentheses represent the number of positive samples/total number of tests.
b Numbers in bold represent months in which >10% positive tests and more than 10 samples were reported.
c Fewer than 10 samples reported in this month.
Monthly data tabulated from all regions monitored within
the state revealed that the onset of the RSV season occurred
either in October or November and ended in March, April,
or May. During 2003-2004 and 2004-2005, the RSV season
lasted six months and during 2005-2006 was seven months
long, beginning in November and ending in May (see Figure 1).
Peak months for RSV activity differed annually and included
February in the 2003-2004 season, January in the 2004-2005
season, and December in the 2005-2006 season. Overall
statewide data yielded a six month RSV season from October
through March with peak activity in January (see Figure 1).
Of interest, in all three time periods there was a noticeable
increase in the percentage of positive RSV tests from June
to July including two seasons in which threshold limits
were exceeded. It is unclear whether this result is a function
of small sample size or high circulating levels of RSV in local
communities. Nevertheless, it indicates that RSV is present in
North Carolina during months outside of the
traditionally-reported season.
Greensboro/Winston-Salem
The four hospitals within this region—Forsyth Medical
Center, High Point Regional Hospital, Moses H. Cone Memorial
Hospital, and Baptist Medical Center—tested 6,438 samples
from inpatients and outpatients, contributing 46.3% of the
total. Combined results from all hospitals in this region revealed
two RSV seasons lasting six months, beginning in either October
or November and concluding in March or April with a peak in
January and a third RSV season of four months with peak
activity in January (see Figure 2).
Wake Medical Center
This facility tested 4,565 samples or 32.8% of the total.
Results showed six month RSV seasons the first two years,
starting in October and concluding in March (see Figure 3).
Unfortunately, data for 2004-2005 were not reported for the
months April through June; therefore it is possible that this
RSV season could have been longer than reported. As with the
first two seasons, the 2005-2006 season started in October but
was of five months duration as the percent of positive RSV tests
dipped to 9.7% in March. In the first season, the peak
lasted essentially for two months, spanning January and
February. In seasons two and three, peak activity occurred in
December (see Figure 3).
Pitt County Memorial Hospital
This hospital contributed 1,139 samples, 8.2% of the total,
over two RSV seasons. Data from this site differs from the others
in that in both time periods the RSV season was short, lasting
three months in 2003-2004, starting in October, and only two
months in 2004-2005, beginning in January (see Figure 4).
Carolinas Medical Center and Hendersonville Pediatrics
Sites in these two regions each participated for one season
and provided 1,778 or 12.8% of the samples. The
Hendersonville practice contributed data for a full year from
NC Med J November/December 2008, Volume 69, Number 6
449
three locations and reported a
seven-month RSV season during
2005-2006 including three
months during which 50% or
more of RSV tests were positive,
including January, the peak
month (see Figure 4). These
findings should be interpreted
cautiously as the high positivity
rates are based on the fewest
number of tests (367) per all
regions and could also reflect a
very strict test screening
process. It is difficult to draw
conclusions for Carolinas
Medical Center as there is no
general pattern to their data,
which was reported over a
period of only eight months.
Figure 1.
RSV Test Data in North Carolina for Years 2003-2006
DISCUSSION
RSV epidemics occur yearly
throughout the United States,
and a select group of infants and young children are at The RSV season in both of these states, and in Hawaii18,19 and
increased risk for severe disease and hospitalization. Results of Alaska,15 is longer than that reported for other parts of the
recent studies provide strong evidence that hospitalizations for country. The National Respiratory and Enteric Virus
RSV-related illness parallel RSV virology data reported in the Surveillance System (NREVSS) has expanded the network of
community.14,15 At the time of our study, the CDC monitored reporting laboratories, and data for the 2007-2008 RSV season
RSV outbreaks through the NREVSS, which consisted of a is available for North Carolina (16 reporting laboratories) and
limited number of laboratories in North Carolina. Data from other states on the CDC website. Several of the laboratories
participating laboratories in individual states that were part of that are currently within the NREVSS network were included
the NREVSS were arbitrarily grouped into four distinct in our study. In contrast to the data now available on the CDC
regions; North Carolina was part of the south reporting region. website with NREVSS-reported data for the entire state, our
Analyses of regional data reported by the CDC indicated that data is regional within North Carolina and statewide. Without
the onset and duration of the RSV season varied substantially knowing the total number of laboratory tests ordered and the
by year and location.10,14
Data were not available Figure 2.
at the state level from RSV Test Data for Greensboro/Winston-Salem Study Sites for Years 2003-2006
the CDC.
Given the variability
in the timing of RSV
outbreaks, there has
been an increase in RSV
surveillance monitoring
at the local level.15,17 At
least 20 state health
departments presently
have some form of RSV
surveillance program.12
Two states—Florida
and Georgia—monitor
RSV in several regions
within their states and
report results on a statesupported website.12,13
450
NC Med J November/December 2008, Volume 69, Number 6
number positive per site, it is
Figure 3.
possible that there could be
RSV Test Data for Wake Medical Center for Years 2003-2006
inherent biases in the
statewide data reported by
NREVSS.
In North Carolina, RSV
prophylaxis is typically given
between November and
March and longer if deemed
medically necessary by the
CDC or a local health
department. For the 20072008 RSV season, North
Carolina Medicaid, the main
provider of palivizumab in
the state, has approved
palivizumab for no more
than five monthly doses,
while some insurance carriers
will reimburse for six doses if
that is supported by virology
data. Our results suggest
that the RSV season in
North Carolina during the
time of our study was at least
six months long, including periods that extended outside of the came from large metropolitan areas. The imbalance of data from
months recommended by the American Academy of Pediatrics these centers could limit generalizations about statewide results.
Our data suggest that the RSV season in regions of North
(AAP) for palivizumab administration.
There are inherent strengths and weaknesses to our study. Carolina may be longer than the national average reported by the
We reported results of almost 14,000 RSV tests, which is a CDC. Additionally, RSV epidemics can persist during months
considerably larger study sample than that reported by other that fall outside of those in which RSV prophylaxis is recommended
investigators.17 RSV activity was monitored from five regions by American Academy of Pediatrics for high-risk children.
within the state over a period of three seasons and included Guidelines on the administration of RSV prophylaxis should
cities with the largest populations within the state. Thus, we ideally be based on results of local RSV test data. NCMJ
were able to determine trends
in RSV activity within some Figure 4.
regions and for the state over RSV Test Data From Each Study Site in North Carolina for Years 2003-2006
time. We acknowledge the
following limitations, which
could have biased study
outcomes. Results of antigen
testing were used to determine
the presence of RSV in
communities as only one site
reported results of viral cultures;
nevertheless, numerous state
health departments and the
NREVSS use similar testing
methodology. The decision to
test individual patients for
RSV was left to the discretion
of each clinician involved in
the study, and data were
reported by month rather than
by week. As can be expected, the
overwhelming majority of data
NC Med J November/December 2008, Volume 69, Number 6
451
Financial Disclosure: MedImmune, Inc.,
provided funding for data management. None
of the participating principal investigators
received any monetary compensation.
Acknowledgment: The authors and North
Carolina RSV Study Team acknowledge the
efforts of Dr. Jay H. Bauman, Scientific and
Technical Evaluation, of Pharmaceuticals, Inc.,
for his analysis and assistance with manuscript
preparation.
North Carolina RSV Study Team
Member
Brent T. Baker, MD
Joy Barwick, MT, (ASCP)
Danny Benjamin, MD, PhD
Rosemary Billings
Louise Hester
Sue Knost, MS, (ASCP)
Cassandra Moran, DO
Elizabeth Palavecino, MD
Mitzi Rumley
David Wilfret, MD
Institution
Hendersonville Pediatrics
Pitt County Memorial Hospital
Duke University
Wake Medical Center
Wake Forest University Baptist Medical Center
Carolinas Medical Center
Duke University
Wake Forest University Baptist Medical Center
Spectrum Lab
Duke University
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