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Research ArticleThe Epidemiology of Upper Respiratory Infections at a TertiaryCare Center: Prevalence, Seasonality, and Clinical Symptoms
Christy S. Stover and Christine M. Litwin
Department of Pathology, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA
Correspondence should be addressed to Christine M. Litwin; [email protected]
Received 16 April 2014; Accepted 30 May 2014; Published 19 June 2014
Academic Editor: Umesh Yadav
Copyright © 2014 C. S. Stover and C. M. Litwin.This is an open access article distributed under the Creative CommonsAttributionLicense, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited.
Improvedmultiplex PCRdetectionmethods are facilitating the correlation of the etiology of respiratory tract infectionswith specificsymptoms or clinical manifestations. We conducted a retrospective analysis of the incidence of respiratory pathogens and initialsymptoms in 1,286 patients at a tertiary care center tested by multiplex respiratory pathogen PCR from July 1, 2012, to June 30,2013. Rhinovirus/enterovirus (Rhino/Entero) infections were the most prevalent (25.4%) followed by respiratory syncytial virus(RSV) (13.6%) and influenza A (6.2%). Eleven percent of patients were positive for multiple analytes with Rhino/Entero and RSVbeing the most common combination. Asthma or asthma exacerbation was the most common presenting symptom in patientspositive for Rhino/Entero (38.4%) or positive for Rhino/Entero along with RSV or hMPV (34.8%). Of the patients positive forRhino/Entero and presenting with asthma, 97% were ≤17 years of age. RSV positive patients most commonly presented withrespiratory distress (40.3%) followed by asthma (18%) or pneumonia (18%). The most prevalent initial clinical manifestation forinfluenza was fever (27.4%) followed by respiratory distress (13%) or pneumonia (11.9%). The significant percentage of patientspositive for Rhino/Entero virus presenting with asthma supports the role of rhinovirus as an important trigger for asthmaexacerbation.
1. Introduction
Acute respiratory tract illnesses are the most frequent ill-nesses of humans and are an important cause of disability anddays lost from school or work [1, 2]. Respiratory infectionsare an important cause of mortality and hospitalization,particularly in the winter in temperate regions. In childrenless than 5 years of age, they are the leading cause of death[3]. Most acute respiratory infections are caused by virusesand bacteria, including rhinoviruses, respiratory syncytialviruses, adenoviruses, influenza viruses, and parainfluenzaviruses.
Many viruses have characteristic seasonal patterns. In-fluenza virus and respiratory syncytial virus (RSV) oftencontribute to the winter peak, but other respiratory virusessuch as human metapneumovirus (hMPV), parainfluenzaviruses (Para), and coronaviruses (CoronaV) also circulatein the fall and winter [4, 5]. Respiratory viruses such asadenovirus (Adeno) and rhinovirus cause illness year-round.An association between these specific respiratory agents and
certain clinical syndromes has been shown to some degree[2]. Knowledge of the clinical signs and symptoms that aremost predictive of the etiologic agent could help physiciansmore accurately diagnose and treat patients in a timelymanner.
The recent increasing use of respiratory pathogen PCRamplification methods in studies of upper respiratory tractinfections has provided new information on the epidemi-ology of respiratory tract infections and has contributed toa better understanding of the seasonality of these etiologicagents and their association with certain clinical manifesta-tions [3, 6, 7]. This study explores the etiology, prevalence,seasonality, and clinical manifestations of upper respiratorytract infections at a tertiary care medical center using a rapidmultiplex PCR respiratory pathogen panel.
2. Methods
Study Participants. Testing took place from July 1, 2012, toJune 30, 2013, on nasopharyngeal specimens (NPS) from
Hindawi Publishing CorporationJournal of Respiratory MedicineVolume 2014, Article ID 469393, 8 pageshttp://dx.doi.org/10.1155/2014/469393
2 Journal of Respiratory Medicine
1,286 patients that were originally sent to Medical College ofGeorgia (MCG) Clinical Microbiology Laboratory (Augusta,GA) from the 500-bed adult and 154-bed pediatric hospitalat MCG for respiratory pathogen PCR assay by the FilmAr-ray Respiratory Panel (RP) (BioFire Diagnostics, Inc., SaltLake City, UT). Nasopharyngeal specimens were obtainedfrom patients with symptoms of a respiratory infection andcollected from the patients according to standard techniqueand placed in viral transport media (Remel MicroTest M4RTViral Transport tube). Specimens were tested as soon aspossible after collection with an average time of 30 minutes.During high volume respiratory season the longest timebetween collection and assay run could be as long as 24 hours.The project was approved by the institutional review board ofour institution; informed consent for the project was waived.Demographic data, such as chief complaint, age, and gender,was obtained for each specimen tested.
FilmArray RP Assay. The FilmArray assay was performedaccording to the manufacturer’s instructions. In brief, 1mLof purified water included in the kit was injected into the Fil-mArray pouch to rehydrate the reagents. Then 300 𝜇L of theviral transport media that had contained the NPS specimenwas mixed with 500𝜇L of sample buffer and then injectedinto the sample port of the pouch.The pouch was then placedinto the FilmArray instrument and a respiratory PCR Panelprogramwas started.The first stage of the program consists ofa multiplexed PCR, followed by an individual nested second-stage real-time PCR contained within a microarray chip. TheFilmArray RP includes two internal controls: an RNAprocesscontrol and controls for every step inside the pouch. Resultsare analyzed using melting curve data.
Theorganism/viruses detected by the FilmArray includedadenovirus, influenza A (FluA), influenza B (FluB), parain-fluenza virus 1 (Para 1), parainfluenza virus 2 (Para 2), par-ainfluenza virus 3 (Para 3), parainfluenza virus 4 (Para 4),respiratory syncytial virus (RSV), coronavirus 229E (Coro-naV 229E), CoronaVNL63, CoronaVHKU1, CoronaVOC43,human metapneumovirus (hMPV), Bordetella pertussis,Chlamydophila pneumoniae, and Mycoplasma pneumoniae.Due to genetic similarity between the human rhinovirusesand enteroviruses, a positive result with PCR primers to theseviruses was listed as Rhino/Entero. The FluA viruses couldalso be subtyped as far as FluA/H1, FluA/H3, or FluA-2009 ifpresent.
2.1. Statistics. A two-sample Student’s 𝑡-test between pro-portions was performed to determine whether there was asignificant difference between the viruses with respect to thepercentage of initial clinical symptoms in both single virusinfections and mixed infections [8]. Statistical analysis wasperformed using the software package StatPac for Windows(Pepin, WI).
3. Results
3.1. Analysis of Positivity Rates and Prevalence within AgeGroups. Specimens from a total of 1,286 patients were ana-lyzed by PCR. The age range of the patients was 3 days
43%
3–6 years
7–21 years
22–49 years8%
13%
20%
16%
≥50 years
≤2 years
Figure 1: Age ranges of study subjects from July 1, 2012, to June 30,2013, MCG.
to 95 years of age, average 14.6 years, median 4 years. Themale : female ratio was 1.30. Rhino/Entero infections werethe most prevalent (25.4%) followed by RSV (13.6%) andinfluenza A (6.2%) (Table 1).
The data was divided according to age groups.The largestage group in our study was that of children ≤2 years oldwith 558 patients (43%) followed by 7–21 age group with 257patients (20%) and 3–6 age group with 201 patients (16%)(Figure 1). The older age groups, 22–49, and ≥50 years weresmaller compared to the first two groups with 101 (8%) and169 (13%) patients in each group, respectively.
The highest total rate of PCR positivity was observedin children 3–6 years of age with a rate of 72.1% (Figure 2)followed closely by 69.9% for the youngest age group, ages≤2.The positivity rate for the older age groups 7–21, 22–49, and≥50 decreased progressively with age, with positivity rates of51.0%, 29.7%, and 29.6%, respectively. The overall positivityrate was 58.0% for one or more viruses.
The highest absolute number of positive cases for thedifferent viruses and bacteria occurred in the ≤2 age group,except for FluB, in which the highest number of casesoccurred in the 7–21 age group. Ninety-eight percent of RSVand 93% of Rhino/Entero cases were detected in patients 21years old or less in age. Nine RSV cases were detected inthe 22–49-year-old group. Three of the nine patients werecoinfected with one other virus, namely, Rhino/Entero, Para1, and CoronaV OC43. One RSV infection occurred in a 49year old patient. Three infections occurred in the ≥50 agegroup. Eighty-three percent of FluA cases and 81% percentof hMPV cases were detected in patients 21 years old or less.Four cases of FluA were detected in the 22–49 age group and10 in the ≥50 age group. Five cases of hMPV were detected ineach of the 22–49 and ≥50 age groups. Seventy-five percentof CoronaV infections were detected in patients 21 years oldor less with 21% of cases (11 patients) occurring in the ≥50 agegroup.
Journal of Respiratory Medicine 3
Table1:Prevalence
ofrespira
tory
pathogenstestedin
different
agegrou
ps:July1,2012,toJune
30,2013.Re
sults
of1,2
86nasoph
aryngealsamples
analyzed
bymultip
lexreal-timePC
Rin
relatio
nto
ageg
roup
.
Analyte
≤2years
3–6years
7–21
years
22–4
9years
≥50
years
Allages
Positivity
rate
Prevalence
(n=558)
Positivity
rate
Prevalence
(n=201)
Positivity
rate
Prevalence
(n=257)
Positivity
rate
Prevalence
(n=101)
Positivity
rate
Prevalence
(n=169)
Positivity
rate
Prevalence
(n=1,2
86)
Rhino/En
tero
152
27.2%
7537.3%
7830.4%
98.9%
137.7
%327
25.4%
RSV
141
25.3%
2110.4%
93.5%
11.0
%3
1.8%
175
13.6%
hMPV
244.3%
105.0%
83.1%
55.0%
53.0%
524.0%
Para
19
1.6%
31.5
%3
1.2%
00%
00%
151.2
%Para
27
1.3%
63.0%
10.4%
11.0
%0
0%15
1.2%
Para
330
5.4%
21.0
%6
2.3%
44.0%
21.2
%44
3.4%
Para
47
1.3%
21.0
%1
0.4%
00%
00%
100.8%
Parainflu
enza
total
539.5
%13
6.5%
114.3%
55.0%
21.2
%84
6.5%
Coron
aV229E
00%
00%
00%
00%
31.8
%3
0.2%
Coron
aVHKU
11
0.2%
00%
00%
00%
10.6%
20.2%
Coron
aVNL6
34
0.7%
21.0
%5
1.9%
00%
00%
110.9%
Coron
aVOC4
322
3.9%
31.5
%2
0.8%
22.0%
74.1%
362.8%
Coron
aviru
stotal
274.8%
52.5%
72.7%
22.0%
116.5%
524.0%
Adenoviru
s16
2.9%
52.5%
31.2
%0
0%1
0.6%
251.9
%Influ
enza
Atotal
285.0%
2210.9%
166.2%
44.0%
105.9%
806.2%
FluA
/H3
285.0%
199.5
%15
5.8%
33.0%
95.3%
745.8%
FluA
/200
9H1
00%
31.5
%1
0.4%
11.0
%1
0.6%
60.5%
Influ
enza
B3
0.5%
63.0%
72.7%
44.0%
53.0%
251.9
%C.
pneumoniae
10.2%
00%
00%
00%
00%
10.08%
M.pneum
oniae
40.7%
21.0
%1
0.4%
00%
10.6%
80.6%
B.pertussis
10.2%
00%
00%
00%
00%
10.08%
Totalp
ositive:
oneo
rmorea
nalytes
390
69.9%
145
72.1%
131
51.0%
3029.7%
5029.6%
746
58.0%
4 Journal of Respiratory Medicine
0
10
20
30
40
50
60
70
80
3–6 7–21 22–49 All ages
Rhino/EnteroRSVParaCoronaVhMPV
AdenoFluA H3FluA H1FluBTotal positivity
Age ranges
Pos
itivi
ty (%
)
≤2 ≥50
Figure 2: Positivity rate in different age groups from July 1, 2012, toJune 30, 2013, MCG.
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0
(%)
B. pertussisC. pneumoniaeM. pneumoniae
hMPVFluA
AdenoCoronaV
ParaRSV
Rhino/Entero
Figure 3: Prevalence of viruses detected in multianalyte positivespecimens from July 1, 2012, to June 30, 2013, MCG. Percent ofmultianalyte positive samples positive for the specific analyte.
The percent positivity rate of the specific viruses withineach age group, however, differed between the age groups(Figure 2). RSV, Para, and Adeno showed the highest preva-lence in the ≤2 age group. Rhino/Entero and FluA virusshowed the highest prevalence in 3–6 age group. Humanmetapneumovirus showed the highest prevalence in both 3–6 age group and 22–49 age group. Influenza B showed thehighest prevalence in 22–49 age group. AndCoronaV showedthe highest prevalence in the ≥50 age group.
Table 2: Viruses or bacteria detected in multianalyte positive sam-ples.
Number Analyte 1 Analyte 2 Analyte 317 RSV Rhino/Entero7 RSV CoronaV OC437 Para 3 Rhino/Entero6 hMPV Rhino/Entero5 FluA/H3 Rhino/Entero4 RSV Para 34 Adeno Rhino/Entero3 RSV Adeno3 RSV M. pneumoniae2 M. pneumoniae Rhino/Entero2 CoronaV NL63 Rhino/Entero2 RSV Para 12 RSV CoronaV NL632 Adeno CoronaV OC432 Adeno FluA/H32 Para 1 Rhino/Entero1 B. pertussis Rhino/Entero1 RSV hMPV1 RSV Para 41 RSV Para 21 Para 3 M. pneumoniae1 Adeno hMPV1 FluB CoronaV NL631 RSV FluA/H31 Para 2 Para 41 CoronaV OC43 Para 31 Rhino/Entero C. pneumoniae1 FluA/H3 M. pneumoniae1 Adeno Rhino/Entero M. pneumoniaeTotal 83
3.2. Analysis of Multianalyte Positive Samples. Fifty-eightpercent of all specimens were positive for at least one viralor bacterial organism. Of the 746 positive specimens, 11%(83/746) had more than one analyte (Table 2). Nearly all(82/83) of the multianalyte positive samples were detected inpatients ≤21 years of age. One patient, 68-year-old patient,described above, was positive for both RSV and M. pneu-moniae. The most common viruses detected in multianalytepositive specimens were Rhino/Entero and RSV. Individually,Rhino/Entero and RSV were detected in all multianalytepositive samples, 57.8% and 50.6% of the time, respectively(Figure 3). There was one triple positive sample (Table 2).
Additional viruses and bacteria found in multianalytepositive samples included Para, hMPV, Adeno, FluA, Coro-naV (NL63, OC43), and M. pneumoniae. The majority ofthe FluA/H3 and hMPV multianalyte positive samples werein conjunction with Rhino/Entero. Also the majority of thePara 3 multianalyte positive samples were in conjunctionwith Rhino/Entero. AllM. pneumoniae infections were found
Journal of Respiratory Medicine 5
0
5
10
15
20
25
30
Num
ber o
f inf
ectio
ns
FluA H3FluBRSV
hMPVRhino/Entero
July1
–14
July15
–28
July29
–Aug
11
Aug12
–Aug
25
Aug26
–Sep
t 8Se
pt9
–Sep
t 22
Sept23
–Oct7
Oct8
–Oct21
Oct22
–Nov
3
Nov
4–N
ov18
Nov
19
–Dec1
Dec2
–Dec15
Dec16
–Dec29
Dec30
–Jan
13
Jan14
–Jan
26
Jan27
–Feb9
Feb10
–Feb23
Feb24
–Mar9
Mar10
–Mar23
Mar24
–Apr6
Apr 7
–Apr20
Apr 21
–May4
May5
–May18
May19
–Jun
e 1Ju
ne2
–Jun
e 15
June
16
–Jun
e 30
July Aug. Sept. Oct. Nov. Dec. Jan. Feb. March April May June
Figure 4: Seasonality of major respiratory viruses from July 1, 2012,to June 30, 2013, MCG. Positive numbers of specific analytes in two-week intervals during the study period, July 1, 2012, through June 30,2013.
FluA H1AdenoPara 3
ParaCoronaV
0Num
ber o
f inf
ectio
ns Para 2Para 1
Para 1
Para 3Para 4
1
2
3
4
5
6
7
8
9
10
July1
–14
July15
–28
July29
–Aug
11
Aug12
–Aug
25
Aug26
–Sep
t 8Se
pt9
–Sep
t 22
Sept23
–Oct7
Oct8
–Oct21
Oct22
–Nov
3
Nov
4–N
ov18
Nov
19
–Dec1
Dec2
–Dec15
Dec16
–Dec29
Dec30
–Jan
13
Jan14
–Jan
26
Jan27
–Feb9
Feb10
–Feb23
Feb24
–Mar9
Mar10
–Mar23
Mar24
–Apr6
Apr 7
–Apr20
Apr 21
–May4
May5
–May18
May19
–Jun
e 1Ju
ne2
–Jun
e 15
June
16
–Jun
e 30
July Aug. Sept. Oct. Nov. Dec. Jan. Feb. March April May June
Figure 5: Seasonality of minor respiratory viruses from July 1, 2012,to June 30, 2013, MCG. Positive numbers of specific analytes in two-week intervals during the study period, July 1, 2012, through June 30,2013.
in conjunction with a virus. The single B. pertussis andC. pneumoniae infections were found in conjunction withRhino/Entero.
3.3. Seasonal Prevalence of Respiratory Pathogens from July 1,2012, to June 30, 2013. The number of cases of the majorand minor viruses was graphed biweekly for the study periodand are represented in Figures 4 and 5. A usually early andfulminant outbreak of FluA started the first week of October,peaked at the end of November and early December, andabruptly decreased by the end of December (Figure 4). Thepeak for the less severe outbreak of FluB cases occurredin March. A distinct peak in RSV cases occurred in earlyDecember, followed by a peak in total CoronaV cases inFebruary and two peaks in hMPV cases in February andApril. The prevalence of Rhino/Entero remained relatively
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
45.0
Asthma/asthma exacerbationRespiratory distressPneumonia
FeverBronchiolitis
Rhin
o/En
tero
and
RSV
or h
MPV
(23
)Rh
ino/
Ente
ro an
d o
ther
pat
hoge
ns(25
)Rh
ino/
Ente
ro(279
)
hMPV
(44
)
RSV
(138
)
Para
(56
)
Cor
onaV
(37
)
Flu
A o
r B(84
)
Case
s with
initi
al cl
inic
al
man
ifest
atio
ns (%
)
Figure 6: Percent of caseswith specific initial clinicalmanifestationsfrom July 1, 2012, to June 30, 2013, MCG.The number in parenthesesis the total number of cases in the group.
high throughout the year with several peak incidences, thehighest occurring in August/September, with three minorpeaks in December, February, and May. Two distinct peaksfor Para 3 cases were observed in December and May(Figure 5). Para 1 cases peaked inOctober andNovember, andPara 2 cases peaked in November. Para 4 cases peaked inMaysimultaneously with Para 3. The 25 cases of Adeno occurredsporadically from September to June. Six cases of FluA H1occurred in March and April.
3.4. Comparison of Initial Symptoms with PCR Diagnosis.The major initial clinical symptoms of the patients includedasthma/asthma exacerbation, respiratory distress, fever, orbronchiolitis. The percentages of these initial symptoms forthe more prevalent respiratory pathogens are presented inFigure 6.
For FluA or B, the most prevalent initial symptom wasfever with 27.4% of patients presenting with this symp-tom. CoronaV positive patients also presented most oftenwith fever (21.6%) followed by respiratory distress. Patientspositive for Para presented with respiratory distress mostcommonly, followed by asthma symptoms.
RSV positive patients most commonly presented withrespiratory distress (40.3%), which was significantly higherthan FluA or B (13%), CoronaV (16.2%), and Para (23.2%)(𝑃 < 0.05). The second most common presenting symptomwas either asthma (18%) or pneumonia (18%).
For hMPV, themost prevalent initial symptomwas pneu-monia, which was a significantly higher incidence thanCoro-naV and Para (27.3%, 𝑃 < 0.05). The second most prevalentinitial symptom was either asthma (22.7%) or respiratorydistress (22.7%).
6 Journal of Respiratory Medicine
Rhino/Entero positive patients initially presented mostoften with asthma symptoms (38.4%) followed by respiratorydistress (31.9%). The percentage of Rhino/Entero positivepatients with asthma was statistically significant when com-pared to FluA or B, CoronaV, Para, and RSV (𝑃 < 0.001).Mixed Rhino/Entero positive cases that were coinfectedwith RSV or hMPV also showed a significantly increasedincidence of asthma when compared to FluA or B andCoronaV (34.8%, 𝑃 < 0.05). Mixed Rhino/Entero positivewith other respiratory pathogens, however, initially presentedmore often with respiratory distress (28%) followed by fever(20%) or asthma (20%) symptoms. Of the patients positivefor Rhino/Entero with symptoms of asthma or asthma exac-erbation, 97% (104/107) were ≤17 years of age and 58.9% were≤6 years of age.
4. Discussion
Over the course of one year, 1,286 nasopharyngeal swabspecimens were analyzed using a respiratory pathogenmulti-plex PCR. We observed characteristic seasonality with RSV,hMPV, FluA and B, CoronaV, and Para, typical for theseviruses. As the age of the patient increased, the positivityrate for the PCR decreased proportionately, starting with apositivity rate of 69.9–72.1% for up to 6 years of age andending with a 30% positivity rate for patients of 22 years orolder. Other studies using multiplex PCR have reported thatpositivity rates decrease proportionately with the age of thepatient [9, 10]. One study showed that older adult patientsshed lower titers of viruses. The lower titers demand theuse of a highly sensitive methodology such as RT-PCR overconventional culture or DFA [11]. The multiplex PCR assaysnow available, however, may still not be sensitive enough todetect the lower titers of virus shed by older adult patients.
Though Rhino/Entero was present throughout the year,there were peaks in the number of cases in September, Jan-uary, March and May. The peaks in September, January, andMarch appear to correspond to the start of school sessionsafter school breaks. Peaks of rhinovirus illness have been welldocumented to occur after school starts in the fall and againin the spring [1, 7, 12].
RSV was the second most prevalent virus, with a verylarge number of cases in January, followed two months laterby an increased number of cases of hMPV in March andMay. This follows the pattern often predicted for hMPV,where the peak number of cases usually occurs after theRSV peak [13–17]. The majority of the RSV infections inour study occurred in children. However, hMPV infectionswere equally distributed among all age groups. We detected apositivity rate of 4.3–5.0% in children up to 6 years of age.This is consistent with other studies, in which hMPV wasdetected in 6% of hospitalized children and 7% of childrenin both outpatient clinics and emergency departments [18].Human metapneumovirus has been known to cause severerespiratory infections in the elderly [19, 20].
The parainfluenza viruses have different patterns of sea-sonal variation based on type. Para 3, which can be pre-dominant in spring in temperate climates, increased in bothDecember and May in our study [21]. Both Para 1 and Para 2
cases were seen only in the fall months in our study, the typi-cal season for these viruses [1]. The epidemiology of Para 4is largely unknown but appeared in May alongside Para 3.The seasonality of the coronaviruses is often dependent ongeographic location [22]. The number of coronavirus casespeaked in February in our study, indicatingwinter seasonalityfor the southeast region. Adenovirus caused illness year-round without any seasonality.
Influenza A started early inOctober, ended inMarch, andpeaked early in December, compared to the overall peak fortheUS in lateDecember. According to theCDC, the influenzaA season was moderately severe, with influenza A (H3N2)viruses predominating [23]. From the week ending February23, 2013, through the end of the season, the FluB was themost commonly reported influenza virus, similar to what wasobserved for the US overall.
Multiple respiratory pathogens were detected in 11%of the specimens with 57.8% of the multianalyte samplesbeing positive for Rhino/Entero, 50.6% positive for RSV, and20.5% positive for both. Rates of multiple-analyte positivespecimens in other studies have also averaged around 8.7–10% [6, 10]. It has been hypothesized that many of the dualpositive RSV and Rhino/Entero samples are due to viralshedding from a previous Rhino/Entero infection [24]. Thepositivity for Rhino/Enteromay also be due to presence of thevirus before symptoms appear. In one study, asymptomaticchildren were often found to be positive for rhinovirus byPCR and thought to be asymptomatic carriers [25].
We, however, observed that patients that were Rhino/Entero positive or Rhino/Entero positive along with RSVor hMPV positive were statistically much more likely topresent with asthma. Rhino/Entero virus infections that werepositive for other viruses or bacteria were more likely topresent with respiratory distress rather than asthma. In onerecent epidemiologic study, rhinovirus was the only virustype significantly associated with asthma exacerbations inchildren aged 2−17 years [26]. The type of respiratory viruslinked to asthma often depends on the age of the patients.Many studies [27] indicate that, in children ≤2 years ofage, RSV predominates, with parainfluenza and rhinovirusas lesser culprits. However, in older children and in adults,rhinovirus accounts for over 50% of viral triggered asthmaexacerbations [28].
Our study found fever symptoms to be significantly high-er in patients positive for influenza than any other virus.It is not surprising that fever is the single most commonpresenting symptom for influenza. Numerous studies haveshown that when influenza is circulating within the commu-nity, patients with fever and cough within 48 hours of onsetof symptoms are likely to have influenza [29–33].
Possible limitations of the study include PCR identifica-tion of an agent that is not necessarily the agent responsiblefor the illness. Rhinovirus is often found at a higher frequencythan any other virus in asymptomatic patients [25]. A con-trol group in which random samples were collected fromasymptomatic patients was not included in the study. Alsosince the study was based at a tertiary care facility, the resultswill be skewed toward the detection of pathogens more often
Journal of Respiratory Medicine 7
associated with severe illness and possibly with the presenceof other chronic conditions, especially in adults.
5. Conclusions
In summary, we observed characteristic seasonality withRSV, hMPV, FluA and B, CoronaV, and Para, typical forthese viruses. Cases of FluA and RSV peaked in December,followed by CoronaV in February, hMPV inMarch, and FluBin April. Parainfluenza viruses peaked in fall, winter, andspring, with Para 1 and Para 2 seen in fall and winter and Para3 and Para 4 in spring. Rhino/Entero was present throughoutthe year, demonstrating peaks in September, January, March,and May.
Asthma was the most common presenting symptom inpatients positive for Rhino/Entero or positive for Rhino/Entero along with RSV or hMPV. This observation supportsthe role of rhinovirus as an important trigger for asthma exac-erbation. RSV positive patients most commonly presentedwith respiratory distress followed by asthma or pneumonia.Themost common initial clinical manifestation for influenzawas fever followed by respiratory distress or pneumonia.
Multiplex PCR has the distinct advantage of allowing forthe ability to quickly and specifically diagnose and treat upperrespiratory tract infections. Rapid and accurate moleculardiagnostic testing methods enhance clinical decision makingand promote the implementation of cost-effective treatmentstrategies, including limiting the use of antibiotics. ActivePCR surveillance can also help predict when seasonal viralepidemics will occur, facilitating the rapid institution ofadditional infection control preventive measures in the hos-pital and clinics. Furthermore, the application of moleculardiagnostic methods for the diagnosis of upper respiratorytract infections has improved our understanding of res-piratory pathogen epidemiology and the common clinicalmanifestations of these diseases.
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper.
Acknowledgment
This study was supported by the Department of Pathology,Medical College of Georgia, Georgia Regents University,Augusta, Georgia.
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