Rapid Infl uenza
Janice K. Louie, Hugo Guevara, Erica Boston,
Melissa Dahlke, Maria Nevarez, Tong Kong,
Robert Schechter, Carol A. Glaser,
and David P. Schnurr
We compared the QuickVue Infl uenza test with PCR
for diagnosing pandemic (H1N1) 2009 in 404 persons with
infl uenza-like illness. Overall sensitivity, specifi city, and
positive and negative predictive values were 66%, 84%,
84%, and 64%, respectively. Rapid test results should be
interpreted cautiously when pandemic (H1N1) 2009 virus
infl uenza at the point of care, many clinicians rely on com-
mercial rapid enzyme immunoassay tests, which are cur-
rently unable to differentiate between infl uenza A virus
subtypes (1). Compared with PCR and viral culture, the
sensitivity of rapid tests for seasonal infl uenza varies from
70% to 90% in children and <40% to 60% in adults (2,3).
The positive and negative predictive values (PPVs and
NPVs) of rapid tests depend on the prevalence of infl uenza
viruses among the population being tested (2,3).
We compare PCR with a rapid infl uenza test to better
characterize the diagnostic utility of the rapid test during
the current pandemic. The QuickVue Infl uenza test (Quidel
Corp., San Diego, CA, USA) detects infl uenza A and B
viruses but does not distinguish between them. Clinicians
may use the test in their offi ces because it is waived from
Clinical Laboratory Improvements Amendment require-
ments based on documentation that test results by persons
without formal laboratory training are in concordance with
results by trained laboratorians.
ince its emergence, the pandemic (H1N1) 2009 virus
has spread rapidly throughout the world. To diagnose
The California Department of Public Health (CDPH)
supplied QuickVue Infl uenza test kits to clinicians partici-
pating in the Centers for Disease Control and Prevention
(CDC) Sentinel Provider Infl uenza Surveillance Program.
Sentinel providers performed the QuickVue Infl uenza test
on a fi rst respiratory specimen obtained from outpatients
with infl uenza-like illness (fever >100°F and cough and/or
sore throat) using the foam swab provided by QuickVue.
Clinicians collected a second respiratory specimen using a
sterile Dacron swab that was stored in viral transport media
at 4°C for <72 hours before shipment to CDPH. Sentinel
providers recorded information about patient demograph-
ics, symptoms, and QuickVue test results on a standardized
specimen collection form.
At CDPH, specimens were tested by an infl uenza A
universal real-time reverse transcription–PCR (rRT-PCR)
assay with an analytical sensitivity (50% tissue culture
infective dose /PCR input) of 0.51 for infl uenza A (4). If
infl uenza A virus nucleic acid was detected, subtyping for
human infl uenza A (H1 and H3) was performed. Speci-
mens negative for any subtype were tested for pandemic
(H1N1) 2009 by using a rRT-PCR detection panel provid-
ed by CDC. For all PCR testing, a cycle threshold (Ct, the
cycle count at which amplifi ed product yielded a detectable
fl uorescent signal) <40 was interpreted as positive. Sensi-
tivity, specifi city, predictive values, likelihood ratios, and
posttest probabilities were estimated according to standard
defi nitions (5). This activity was reviewed by the California
Committee for the Protection of Human Subjects and de-
termined to be a public health response that did not require
institutional review board approval.
From May 4 to November 19, 2009, a total of 703
specimens were collected, including swabs from nares
(293), nasopharynx (178), oropharynx (3), a mixture of
sites (227), and unspecifi ed sites (2). During this same peri-
od, statewide surveillance detected pandemic (H1N1) 2009
in 30%–50% of patients with infl uenza-like illnesses tested
and 92%–100% of infl uenza viruses identifi ed.
The median age of patients with infl uenza-like illness
was 19 years (range 0–80 years). The median time from
illness onset to specimen collection was 2 days (range 0–20
days). Of 703 specimens tested, 417 came from patients
who had positive PCR results for infl uenza; 13 had sea-
sonal infl uenza A subtypes, including 9 A/H1 and 4 A/H3;
and 404 patients had pandemic (H1N1) 2009. Of these 404
patients, 266 (66%) had positive results and 138 (34%) had
negative results by rapid antigen test (Table). Of 299 pa-
tients in which pandemic (H1N1) 2009 was not detected
by PCR, 49 (16%) were positive and 250 (84%) were nega-
tive by the rapid antigen test. The prevalence of pandemic
(H1N1) 2009 infection in all samples was 57%. The over-
all sensitivity, specifi city, PPV, and NPV of the QuickVue
Infl uenza Rapid Test for 2009 (H1N1) infl uenza when
compared with PCR, regardless of the timing of collec-
tion, were 66%, 84%, 84%, and 64%, respectively, with a
positive test result increasing the posttest probability from
824 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 5, May 2010
Author affi liation: California Department of Public Health, Rich-
mond, California, USA
Rapid Antigen Test for Pandemic (H1N1) 2009
57% to 84% and a negative test result decreasing it to 36%.
The sensitivity, specifi city, PPV, and NPV of the rapid test
compared to PCR for persons <18 years of age were 68%,
80%, 87%, and 56%, respectively, and for persons >18
years were 64%, 86%, 82%, and 69%, respectively.
Ct values were available for 389 specimens in which
pandemic (H1N1) 2009 virus was detected by PCR; of
these, the median infl uenza A PCR Ct value was 26 for
135 specimens with a negative rapid test result and 21 for
254 specimens with a positive rapid test result (p<0.0001);
samples with higher viral loads were more likely to be posi-
tive by rapid test (Figure). Even so, ≈25% of PCR-positive,
rapid test–negative specimens had Ct values <23.
Other smaller studies have found comparable sensitiv-
ities, but higher specifi cities, for rapid antigen tests for pan-
demic (H1N1) 2009. In a CDC study of 45 samples provid-
ed by state laboratories, the sensitivity of all rapid tests was
40%–69%, including 69% for QuickVue Infl uenza A+B
(6). Others have found the QuickVue rapid tests to have
sensitivities of 51%–63% and specifi cities of 99%–100%
(7–9). During a large cluster of school outbreaks in New
York, NY, USA, the sensitivity and specifi city of the Bi-
nax NOW (Inverness Medical International, Bedford, UK)
rapid test were 17.8% and 93.6%, respectively (10). As we
found, positive rapid antigen test results in other studies
also appear to correlate with higher concentrations of pan-
demic (H1N1) 2009 virus (6,11,12).
Our fi ndings illustrate the challenges clinicians face
during the current pandemic. Because clinical symptoms of
pandemic (H1N1) 2009 are nonspecifi c, defi nitive diagno-
sis requires confi rmatory PCR testing, which, when avail-
able, often requires several days between specimen col-
lection and reporting of results. Rapid antigen tests are the
only current option for screening and diagnosis at the point
of care. Current CDC guidelines recommend that high-
risk and hospitalized infected patients be treated promptly
with antiviral drugs and managed by using specifi c infec-
tion control precautions (13). Given the frequency of error
found in this study, pandemic (H1N1) 2009 cannot be ex-
cluded solely because of a negative rapid antigen test result.
Likewise, false-positive results, which would be expected
to increase when the prevalence of infl uenza as a cause of
infl uenza-like illness decreases, may result in unwarranted
treatment and infection control measures that can be labor
and resource intensive. Although rapid antigen tests are re-
ported to have high specifi city for seasonal infl uenza, our
fi ndings confl ict with previous assumptions that rapid an-
tigen tests are suffi ciently specifi c to guide decisions about
withholding antiviral treatment or chemoprophylaxis for
pandemic (H1N1) 2009 (2).
A difference in swab types between rapid and PCR
testing might have affected sensitivity of the rapid test re-
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 5, May 2010 825
Table. Performance of rapid antigen test compared with PCR in the diagnosis of pandemic (H1N1) 2009*
No. rapid test positive, PCR positive
No. rapid test positive, PCR negative
No. rapid test negative, PCR positive
No. rapid test negative, PCR negative
Total no. tested
Prevalence of PCR positives in sample
Positive predictive value
Negative predictive value
Positive likelihood ratio (95% CI)
Posterior probability of positive test result (95% CI)
Negative likelihood ratio (95% CI)
Posterior probability of negative test result (95% CI)
*CI, confidence interval.
†Does not include results for 15 case-patients where age was not recorded.
Patient age <18 y†
Patient age >18 y†
Figure. Comparison of cycle threshold (Ct) values for pandemic
(H1N1) 2009 real-time reverse
specimens (n = 389) with negative (neg) and positive (pos) rapid
antigen test (RT) results. Solid lines represent median value for Ct.
sults. Likewise, although infl uenza B virus was detected in
only 9 (0.09%) of 10,367 specimens during the 7.5 months
of statewide surveillance, some rapid test results may have
been interpreted as falsely positive due to infection with
infl uenza B.
In conclusion, we found the QuickVue infl uenza test
had suboptimal sensitivity and specifi city for the detection
of pandemic (H1N1) 2009 during a period of increased
prevalence in California. This fi nding suggests that rapid
test results that may lead to changes in clinical management
or public health intervention should be confi rmed with
PCR. A strength of our study is its refl ection of typical test-
ing practices in outpatient settings and the need for recon-
sideration of the clinical application of rapid test results.
The development of more accurate point-of-care tests for
seasonal and pandemic (H1N1) 2009 infection is urgently
We thank Estela Saguar, Ricardo Berumen, Emily Hunley,
Pan Chao, Elaine Yeh, Sharon Messenger, Meileen Acosta, David
Cottam, Ray Sante, and Anthony Moore for assistance with vari-
ous aspects of laboratory testing and surveillance. Additionally,
we gratefully acknowledge the contributions of participating sen-
tinel providers and staff at California local health departments and
local public health laboratories, who diligently work to provide
the epidemiologic and clinical data and submit specimens to the
California Department of Public Health.
Dr Louie is chief of the Infl uenza and Respiratory Diseases
Section at the California Department of Public Health. Her re-
search interests include characterization of the epidemiology and
virology of infl uenza and other respiratory viruses.
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Address for correspondence: Janice K. Louie, California Department of
Public Health, 850 Marina Bay Pkwy, Richmond, CA 94804, USA: email:
826 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 5, May 2010
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