M A J O R A R T I C L E
A Cluster of Patients Infected With I221V
Influenza B Virus Variants With Reduced
Oseltamivir Susceptibility—North Carolina and
South Carolina, 2010–2011
Shikha Garg,1,2Zack Moore,3Nicole Lee,3John McKenna,2Amber Bishop,2Aaron Fleischauer,3Chasisity B. Springs,4
Ha T. Nguyen,2Tiffany G. Sheu,2Katrina Sleeman,2Lyn Finelli,2Larisa Gubareva,2and Alicia M. Fry2
1Epidemic Intelligence Service and2Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and
Prevention, Atlanta, Georgia;3North Carolina Department of Health and Human Services, Raleigh; and4South Carolina Department of Health and
Environmental Control, Columbia
(B/I221V), associated with reduced in vitro oseltamivir susceptibility were detected in North Carolina.
Methods.We determined the prevalence of I221V among B viruses submitted to the Centers for Disease
Control and Prevention for antiviral resistance surveillance, including all B viruses submitted to North Carolina
and South Carolina state laboratories, during October 2010–September 2011.We conducted chart reviews and
telephone interviews to characterize North Carolina and South Carolina patients with B/I221V vs wild-type B
virus infection (B/WT).
Results. We detected I221V in 45 (22%) of 209 B viruses from North Carolina and 8 (10%) of 82 B viruses
from South Carolina. We detected I221V in 3 (0.3%) of 881 B viruses tested from 45 other states. B/I221V infection
was not associated with differences in underlying conditions or illness severity, compared with B/WT infection. No
patients with B/I221V infection received oseltamivir prior to specimen collection. Among patients who completed
oseltamivir, those with B/I221V infection reported a longer duration until illness resolution (5 vs 3 days; P=.02).
Conclusions. B/I221V cocirculated with B/WT in North Carolina and South Carolina during 2010–2011. I221V
did not alter illness severity but may have reduced oseltamivir effectiveness. Thus, global surveillance for I221V is
During 2010–2011, influenza B viruses with a novel neuraminidase substitution, denoted I221V
Keywords. influenza B virus; neuraminidase substitution; oseltamivir; antiviral resistance.
Influenza B viruses cause annual epidemics and can
be associated with severe disease resulting in hospitali-
zations and deaths [1–3]. Neuraminidase (NA) inhibi-
tors (NAIs), including oseltamivir and zanamivir, are
the only class of antiviral agents currently licensed to
treat influenza B virus infections. The Centers for
Disease Control and Prevention (CDC) and the World
Health Organization Global Influenza Surveillance
program conduct year-round surveillance to monitor
for susceptibility of circulating influenza viruses to an-
tiviral agents in the United States and globally.
During the 2010–2011 influenza season, through
routine surveillance, the CDC influenza laboratory
identified a cluster of influenza B viruses from North
Carolina with an elevated median inhibitory concen-
tration (IC50) to oseltamivir on a functional NA inhi-
bition (NI) assay, interpreted as reduced susceptibility
to oseltamivir, when compared with reference influen-
za B viruses . All influenza B viruses in this cluster
were found by sequencing to have a novel NA substi-
tution, denoted I221V .
Received 30 July 2012; accepted 17 October 2012; electronically published 13
Presented in part: 49th Annual Infectious Diseases Society of America
Meeting, Boston, Massachusetts, 2011. Abstract 932.
Correspondence: Shikha Garg, MD, MPH, 1600 Clifton Rd, Mailstop E46,
Atlanta, GA 30333 (sGarg1@cdc.gov).
The Journal of InfectiousDiseases2013;207:966–73
© The Author 2013. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
966 • JID 2013:207 (15 March) • Garg et al
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Prior to this cluster, influenza B viruses with NA substitu-
tions associated with reduced oseltamivir susceptibility had
been rarely described [5–11]. We sought to characterize the
epidemiologic and clinical characteristics of patients infected
with influenza B viruses with the I221V substitution (B/
I221V) as compared to patients infected with influenza B
viruses without the I221V substitution (B/wild-type). We
further sought to evaluate the clinical effectiveness of oselta-
mivir among patients infected with B/I221V viruses.
During the 2010–2011 influenza season, states were requested
to send a sample of 5 influenza viruses, representing a mixture
of circulating types and subtypes, to the CDC every 2 weeks
for routine antiviral resistance surveillance. During routine
drug susceptibility testing, several influenza B viruses from
North Carolina were found by in vitro assays to have reduced
oseltamivir susceptibility. When sequenced, a novel mutation,
I221V (ATC→GTA), consisting of an isoleucine (I) to valine
(V) substitution at position 221 (B NA numbering corre-
sponds to 222 in the N2 NA amino acid numbering) was de-
tected in a conserved residue of the NA active site of these
influenza B viruses . After the cluster of B/I221V viruses
was identified , we requested that all influenza B viruses
submitted to North Carolina and South Carolina state public
health laboratories be sent to the CDC for expanded B/I221V
testing. In addition, all virus isolates submitted to the CDC for
antiviral resistance surveillance from 44 other state public
health laboratories were tested for this marker by conventional
sequencing and/or pyrosequencing [4, 9].
An epidemiologic investigation was initiated in North Caroli-
na and South Carolina, the states where B/I221V viruses were
identified. Information on age, sex, specimen collection date,
and county of residence was obtained from laboratory requisi-
tion forms of all patients with influenza B virus infections
who had clinical specimens submitted to state public health
laboratories in North Carolina and South Carolina during
October 2010–March 2011. Healthcare providers who submit-
ted clinical specimens that were subsequently tested for B/
I221V were asked to complete standardized medical record
abstraction forms that included information on past medical
history, details of the influenza illness at the time of the
clinic visit, prescribed treatment, and any clinical outcomes
that were known. Standardized telephone interviews were also
attempted for all patients or for their parent or guardian, for
whom contact information was available. Patients were asked
details about their influenza illness, potential exposures
related to their influenza illness, and whether they completed
oseltamivir treatment. Patient surveys were translated into
Spanish, and all interviews were conducted in Spanish for pa-
tients who spoke Spanish as their primary language. All tele-
phone interviews were conducting in March 2011. Calendars
and medical office visit dates were used as memory aids
during the interview.
The CDC determined that this investigation represented a
public health response and did not require institutional review
board authorization. All patients who were contacted as part
of the investigation were given the opportunity to decline the
We used t tests and Wilcoxon rank sum tests, for continuous
variables, and χ2tests and Fisher exact tests, for categorical
variables, to compare clinical and epidemiologic characteristics
between patients infected with B/I221V and B/wild-type
viruses. Among a subset of patients who reported completing
a course of oseltamivir treatment, we also compared treatment
effectiveness between patients with B/I221V infection and
those with B/wild-type infection. Many factors potentially
biased receipt and completion of antiviral treatment, including
severity of illness, age, time since illness onset, socioeconomic
factors, and underlying conditions . Since we did not
collect all of these data systematically and had a small sample,
we did not attempt to compare antiviral treatment effective-
ness between treated and untreated patients. We assumed
these biases did not affect comparison of clinical outcomes
between treated patients with B/I221V and those with B/wild-
type infection, because clinicians were unaware of I221V
status. A 2-tailed P value of≤ .05 was considered statistically
significant. Analyses were performed in SAS, version 9.2
Prevalence of B/I221V Viruses
During October 2010–September 2011, the prevalence of
I221V among influenza B viruses from patients who had clini-
cal specimens submitted for surveillance was 22% (45 of 209)
in North Carolina and 10% (8 of 82) in South Carolina. The
I221V substitution was also detected in 3 (0.3%) of 881 B
viruses tested from 45 other states; this includes 1 virus (6%)
among 17 tested from Florida and 2 viruses (2.2%) among 91
tested from New York. The individual from Florida had no
epidemiologic links or travel to North Carolina or South Car-
olina, and epidemiologic links were not identified for the 2
individuals from New York. Within North Carolina and South
Carolina, most B/I221V viruses were detected from an area
surrounding Charlotte, North Carolina, near the North Caro-
lina/South Carolina border (Figure 1). B/I221V was detected
in clinical specimens from residents of 15 counties and
I221V Influenza B Virus Infections • JID 2013:207 (15 March) • 967
by guest on November 1, 2015
accounted for >40% of influenza B virus infections in 7 of
All B/I221V viruses were of the Victoria lineage and were
antigentically similar to the influenza B virus strain contained
within the 2010–2011 influenza vaccine . In a previous pub-
lication, we reported that phylogenetic analysis showed that
the B/I221V viruses from North Carolina formed a distinct
cluster within the NA gene of Victoria lineage B viruses; no
such cluster was observed in the HA gene . Furthermore,
no additional mutations were exclusively or consistently ob-
served in the NA gene of the B/I221V viruses. Use of the fluo-
rescentNA inhibition assay
oseltamivir IC50of the B/I221V viruses (19.86 nM) was 6-fold
greater than that of the CDC reference wild-type oseltamivir-
susceptible influenza B viruses (3.25 nM) and 2-fold higher
than that of the B/wild-type influenza viruses circulating in
North Carolina and South Carolina during 2010–2011 (8.33
nM) . Virologic details are described fully elsewhere .
and South Carolina (SC), October 2010–September 2011 (n =291). A, Within North Carolina and South Carolina, areas colored in white indicate that no
influenza B virus clinical specimens were received by state public health laboratories from these counties. The star represents the location of Charlotte,
North Carolina. B, Within each county, the numerator represents the number of cases of B/I221V infection, and the denominator represents the total
number of influenza B virus clinical specimens that were submitted to the state public health laboratory.
Detection of influenza B viruses with I221V, by state and county, among patients with influenza B virus infections—North Carolina (NC)
968 • JID 2013:207 (15 March) • Garg et al
by guest on November 1, 2015
B/I221V was first detected in an influenza B virus from a
North Carolina patient on 10 November 2010 and was last
detected in an influenza B virus from a South Carolina patient
on 28 February 2011 (Figure 2). There was some clustering of
B/I221V-infected patients among students at a college in
North Carolina (4 persons infected during 24 January 2011–
27 January 2011; 2 persons infected during 7 February 2011–
9 February 2011) and a college in South Carolina (3 persons
infected during 21 February 2011–28 February 2011).
Nationally, during the 2010–2011 influenza season, 74% of
circulating influenza viruses were influenza A viruses, and
26% were influenza B viruses. While the proportion of circu-
lating viruses in South Carolina that were influenza B (32%)
was similar to the national estimate, the proportion of influen-
za viruses in North Carolina that were influenza B (42%) was
higher than seen nationally . Among 742 influenza B
viruses tested nationally, 699 (94%) belonged to the B/Victoria
lineage, and 43 (6%) belonged to the B/Yamagata lineage. The
distribution of B/Victoria vs B/Yamagata viruses in North Ca-
rolina and South Carolina was similar to that seen nationally
. Peak influenza-like activity was higher than the national
peak (4.5%) for both South Carolina (7%) and North Carolina
(6%) during the 2010–2011 season.
Epidemiologic and Clinical Characteristics of Patients With
Influenza B Virus Infections
The North Carolina and South Carolina state public health
laboratories identified influenza B virus in clinical specimens
from 302 patients during the 2010–2011 influenza season.
Specimens from 291 (96%) of these patients were tested by
conventional sequencing and/or pyrosequencing for I221V. Of
these 291 patients, we sought to conduct medical record
reviews and telephone interviews for 233 (80%) patients. In
South Carolina, of 82 patients tested for I221V, we sought to
interview 24 patients from counties in South Carolina where
B/I221V was known to be circulating, because of limited re-
sources. Medical record reviews and telephone surveys were
completed for 168 patients (72%; 149 from North Carolina
and 19 from South Carolina). Medical records were used in
lieu of telephone interviews for patients who had cognitive
dysfunction (n= 2) or were deceased (n = 7).
There were no significant differences in age, sex, or underly-
ing medical conditions of patients infected with influenza B
viruses with and those infected with influenza B virus without
I221V (Table 1). The majority of patients with influenza B
virus infections were younger than 30 years and enrolled in
prekindergarten–fourth grade (38%) or college (53%). A sig-
nificantly higher proportion of patients with B/I221V infec-
tion spoke only Spanish, compared with patients infected with
B/wild-type viruses (33% vs 20%; P≤ .05).
No patients infected with influenza B viruses with or with-
out I221V had received oseltamivir for prophylaxis or treat-
ment prior to collection of their specimen for influenza testing
(Table 1). A small number of patients in both groups reported
exposure prior to specimen collection to a household contact
who was receiving oseltamivir. About half of the patients in
both groups reported exposure to a sick contact at school or
work. Nine patients with B/I221V infection were college
Carolina (NC) and South Carolina (SC), October 2010–September 2011 (n=291).
Epidemic curve of influenza B virus infections, by week, and percentage of infected individuals who tested positive for I221V—North
I221V Influenza B Virus Infections • JID 2013:207 (15 March) • 969
by guest on November 1, 2015
students at a single university in North Carolina, and 5 were
college students at a single university in South Carolina. These
patients had no other epidemiologic exposures in common.
Two patients from South Carolina had traveled prior to illness
onset to a North Carolina county in which B/I221V was cir-
culating; one was found to be infected with a B/I221V virus.
The median number of days from illness onset to influenza
specimen collection was 2 days for patients infected with in-
fluenza B virus with and those infected with influenza B virus
without I221V (Table 2). Among all patients, 94% took over-
the-counter antipyretic medications to treat their symptoms.
There were no significant differences in the proportion of pa-
tients infected with B/I221V virus as compared to B/wild-type
virus who had fever, cough, sore throat, or other symptoms
associated with their infection. There were also no significant
differences in the proportion of patients who missed school or
work as a result of illness, required additional office visits,
were hospitalized as a result of their illness, or died.
Effectiveness of Oseltamivir
On the basis of data obtained from patient interviews, 14 of
38 patients (37%) with B/I221V infection and 75 of 128 pa-
tients (59%) with B/wild-type infection confirmed starting
With Influenza B Virus Infection—North Carolina and South
Carolina, October 2010–March 2011
Clinical Illness and Outcomes Among 233 Patients
Time from illness onset to
evaluation, d, median (range)a
School or work missed
Facility type where care was sought
Urgent care center
Extra medical visits needed
Length of stay, d, median
2 (0–15)2 (0–17)
Data are proportion (%) of patients for whom the specified characteristic was
present, unless otherwise indicated. P values were nonsignificant for all
Abbreviation: ICU, intensive care unit.
aData are for 51 patients with B/I221V and 182 with B/wild-type.
bData are for 4 patients hospitalized with B/I221V and 22 patients
hospitalized with B/wild-type virus infection.
Infection—North Carolina and South Carolina, October 2010–
Characteristics of 233 Patients With Influenza B Virus
Grade in school
Influenza vaccination in 2010–2011
Underlying medical condition(s)c
Long-term care facility
Travel ≤7 d before illness onset
Sick contact at school
Sick contact at work
Known household contact of an
individual receiving oseltamivire
26/51 (51) 97/182 (53)
Data are proportion (%) of patients for whom the specified characteristic was
present, unless otherwise indicated.
Abbreviation: PreK, prekindergarten.
aData are for 51 patients with B/I221V and 182 with B/wild-type.
cAsthma, chronic lung disease, neurologic condition, cardiac
disease, diabetes mellitus, hepatic disease, renal disease, and/or
dIn the 2 weeks prior to specimen collection for influenza virus
eIn the week prior to specimen collection.
970 • JID 2013:207 (15 March) • Garg et al
by guest on November 1, 2015
oseltamivir treatment for their influenza episode. Among pa-
tients who started oseltamivir treatment and with available
data on oseltamivir completion, 12 of 14 (86%) with B/I221V
infection and 61 of 75 (81%) with B/wild-type infection re-
ported completing the entire course of oseltamivir treatment
Among the 12 patients with B/I221V infections and 61 pa-
tients with B/wild-type infections who completed oseltamivir
treatment, a similar proportion took antipyretic medications
for their illness (Table 3). Among patients who completed
oseltamivir treatment, those with B/I221V infection reported
significantly longer intervals between the date of their initial
physician visit and the time they felt better and the time they
felt like themselves, compared with patients with B/wild-type
infection. The duration of several clinical symptoms was
longer and more days of work or school were missed among
patients with B/I221V infection; however, no values were sig-
nificantly different from those for patients with B/wild-type
infection. In contrast, among patient who did not receive osel-
tamivir treatment, the duration of most symptoms and illness
did not differ between patients with B/I221V and B/wild-type
infections, except for days of school or work missed. Among
the 73 patients who completed oseltamivir treatment, 64
(88%) had information available on timing of oseltamivir
treatment, and all reported starting oseltamivir on the same
day as their initial physician visit. Patients who reported com-
pleting only partial treatment with oseltamivir (duration, 1–4
days) were excluded.
Update for the 2011–2012 Influenza Season
During 1 October 2011–31 March 2012, none of the 132 in-
fluenza B viruses tested from 41 states for antiviral resistance
were found to have the I221V mutation, including 3 influenza
B viruses tested from North Carolina. Only 64 (42%) of the
152 influenza B viruses tested during 2010–2011 belonged to
the Victoria lineage, while 88 (58%) belong to the Yamagata
We describe the epidemiologic and clinical characteristics of a
large cluster of individuals infected with influenza B viruses
with reduced oseltamivir susceptibility and a novel I221V NA
substitution. B/I221V viruses cocirculated with wild-type in-
fluenza B viruses in 1 geographic region in the United States
throughout the 2010–2011 influenza season. These B/I221V
viruses circulated in the absence of drug pressure. We found
no evidence to suggest that B/I221V viruses behaved differ-
ently than B/wild-type viruses with respect to populations af-
fected or illness severity Although the number of oseltamivir-
treated patients in our analysis was small, our data suggest
that oseltamivir may have had less effect on reducing illness
among those infected with B viruses with the I221V
This is the first cluster of influenza B viruses with an NA
substitution and reduced oseltamivir susceptibility to be re-
ported. Prior reports have described the prevalence of influen-
za B viruses with substitutions at the 221 residue to be rare [6,
10]. Amino acid 221 is a highly conserved residue of the NA
enzyme active site. I221T has been reported sporadically from
surveillance [6, 14]; however, the viruses from this investiga-
tion are the first report of I221V . NA substitutions among
influenza B viruses have been detected only sporadically
Receive Oseltamivir Treatment —North Carolina and South Carolina, October 2010–March 2011
Clinical Illness and Outcomes Among 149 Patients With B Virus Infection Who Completed Oseltamivir Treatment or Did Not
Completed Oseltamivir TreatmentDid Not Receive Oseltamivir Treatment
B/I221V (n= 24)
Antipyretic use, no.
Fever duration, d
Cough duration, d
Sore throat duration, d
Chills duration, d
Myalgias duration, d
Extra medical visits, no.
School/work time missed, d
Time until feeling better, d
Time until feeling like self, d
Data are no. (%) of subjects or median value (range).
I221V Influenza B Virus Infections • JID 2013:207 (15 March) • 971
by guest on November 1, 2015
through global antiviral resistance surveillance [7, 9, 11, 14, 15]
and have been reported rarely among influenza B virus speci-
mens from patients after receipt of NAI therapy [5, 6, 8]. Al-
though it is not possible to know whether B/I221V viruses
initially emerged spontaneously or in relation to drug pres-
sure, the lack of exposure to oseltamivir prior to specimen col-
lection among patients infected with B/I221V viruses suggests
that the substitution may not have developed in response to
oseltamivir use. In vitro studies and animal models have
found that NA substitutions may affect NA activity and com-
promise the ability of the virus to infect individuals and cause
disease. [16, 17]. However, our investigation suggests that the
presence of the I221V substitution did not compromise the
ability of influenza B viruses to cause illness or to be transmit-
ted efficiently within populations. Furthermore, B/I221V
viruses infected people with similar demographic characteris-
tics and caused similar illness as wild-type influenza B viruses.
In vitro functional NI assays revealed that all B/I221V
viruses had an elevated IC50to oseltamivir, compared with ref-
erence viruses . Notably, wild-type, oseltamivir-susceptible
influenza B viruses have a higher baseline IC50 for oselta-
mivir than do influenza A viruses [14, 18, 19]. Several studies
have questioned whether the higher baseline IC50values trans-
late into altered drug effectiveness [20–22]. A few observation-
al studies have suggested that oseltamivir may reduce fever
quicker in patients with influenza A virus infections, com-
pared with patients with influenza B virus infections [20–22].
Thus, a NA substitution, such as I221V, that increased the
IC50in influenza B viruses even higher might be clinically im-
portant. Our findings suggest that patients with uncomplicat-
ed illness due to B/I221V infection may not have responded
to oseltamivir treatment as effectively as patients with B/wild-
type virus infection, as evidenced by a longer duration from
initiation of antiviral therapy to illness resolution. A trend
toward a longer duration of several clinical outcomes suggests
these findings may not be spurious. However, we cannot
exclude the possibility of random effects from multiple com-
parisons in a small sample, and we were not able to compare
treated and untreated patients, since we did not collect infor-
mation on biases related to antiviral receipt. Although we were
not able to assess the effectiveness of oseltamivir treatment for
severe B/I221V infection, our findings suggest that oseltamivir
may not be optimal treatment for severe infections due to B/
I221V. Because of the high prevalence of B/I221V at the time
of the investigation and the uncertain clinical significance of
the in vitro finding of reduced oseltamivir susceptibility, the
North Carolina Department of Health and Human Services
alerted clinicians about the cluster and advised them to con-
sider this information when treating patients with severe influ-
enza B virus infections who did not appear to be responding
to oseltamivir. Intravenous zanamivir, an investigational
agent, was recommended as an alternative treatment.
Influenza B viruses can be associated with severe disease
[1–3], and in this investigation, a total of 26 patients with in-
fluenza B virus infection were hospitalized as a result of their
influenza episode, 10 patients required intensive care unit ad-
mission, and 7 patients died. Although numbers were small,
there were no significant differences in the proportion of pa-
tients with B/I221V vs B/wild-type who were hospitalized,
required intensive care unit admission, or died. In accordance
with guidelines, all individuals >6 months of age should
receive influenza vaccination annually to prevent complica-
tions associated with influenza virus infection [23, 24].
This investigation had several limitations. The number of
influenza specimens submitted for surveillance varied by state
and county, and several counties submitted no specimens;
thus, the prevalence of B/I221V viruses could have been
higher and the circulation more widespread than we describe.
A higher proportion of patients infected with B/I221V spoke
only Spanish. Thus, it is possible that there were epidemiolog-
ical links that we were unable to identify during the investiga-
tion and that there may have been more localized circulation
of B/I221V. Clinical illness information was collected retro-
spectively after resolution of influenza, and patient memory
regarding certain clinical details may have declined over time;
however, we used calendars and medical office visit dates as
memory aids and medical record data to corroborate patient
information. Finally, given the small sample size, there was
limited power to detect clinically significant differences in
illness course and outcomes among patients infected with in-
fluenza B viruses with and viruses without I221V.
Influenza B viruses with reduced oseltamivir susceptibility
and a novel NA substitution cocirculated with wild-type influ-
enza B viruses in a limited geographic area within the United
States during the 2010–2011 influenza season. As of 31 March
2012, no B/I221V viruses were detected during the 2011–2012
influenza season, although circulation of Victoria-like B
viruses was low. Thus, it appears unlikely that influenza B
viruses with the I221V substitution will circulate more widely
in the near future. However, the ability of B/I221V viruses to
be transmitted within the community, their unaltered ability
to cause human illness, and the possible effect of the NA sub-
stitution on the clinical effectiveness of oseltamivir, make any
future widespread circulation of B/I221V viruses concerning.
Thus, surveillance for NA substitutions at the 221 residue
should be included in global surveillance for antiviral resis-
tance among influenza B viruses.
Supplementary materials are available at The Journal of Infectious Diseases
online (http://jid.oxfordjournals.org/). Supplementary materials consist of
data provided by the author that are published to benefit the reader. The
posted materials are not copyedited. The contents of all supplementary
972 • JID 2013:207 (15 March) • Garg et al
by guest on November 1, 2015
data are the sole responsibility of the authors. Questions or messages
regarding errors should be addressed to the author.
South Carolina, as well as the county health departments in North Caroli-
na and South Carolina, for their assistance with this investigation. We also
thank the following individuals for their contributions: N. Janine Dailey
Garnes, Susan Kilpatrick, and Peggy Brantley (North Carolina Department
of Health and Human Services, Raleigh, NC); Jennifer Meredith (South
Carolina Department of Health and Environmental Control (Columbia,
SC); Matthew Biggerstaff and Krista Kniss (Influenza Division, National
Center for Immunization and Respiratory Diseases, Centers for Disease
Control and Prevention, Atlanta, GA); Rob Garmin (Tennessee Depart-
ment of Health, Nashville, TN); and Kirstin St George and Jennifer La
Plante (New York State Department of Health, Albany, NY).
The findings and conclusions in this report are those of
the authors and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.
Financial support. This work was supported by the Centers for Disease
Control and Prevention.
Potential conflicts of interest.
All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
We thank the residents of North Carolina and
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