Department of Virology, School of Public Health, Tehran University of Medicalciences, Tehran, IranDepartment of Biochemistry, Faculty of Medicine, Iran University of Medicalciences, Tehran, IranDepartment of Pediatrics, University Medical Center Utrecht, Utrecht, TheetherlandsDepartment of Immunology, University Medical Center Utrecht, Utrecht, Theetherlands
eceived 2 March 2015; received in revised form 14 April 2015; accepted 2 May 2015
Summary Respiratory syncytial virus (RSV) is a leading cause of acute respiratoryinfection during early childhood and is associated with a great burden on patients,parents, and society. While no treatment is yet available, results from recent phase2 clinical trials of cell-entry inhibitors and RSV vaccines are promising. To preparefor introduction of these novel therapeutics, good understanding of its molecularepidemiology and continuous RSV surveillance data are necessary. This paper pro-vides an overview of RSV prevalence and genotype distribution in Iran from 1996
Iranto 2013. This meta-analysis includes 21 published studies. In total, 775 (18.7%) of4140 respiratory specimens were positive for RSV infection. The male-female ratioof RSV-positive patients was 1.5:1. Significant peaks of RSV infection were detectedduring the cold season (November—March). RSV infection was mainly observed inpatients <2 years of age. Phylogenetic studies showed that genotypes GA1, GA2, GA5,
and BA co-circulated in Iran in 2007—2013. This review highlights the necessity of
Abbreviations: RSV, respiratory syncytial virus; Flu, influenza; PIV, parainfluenza; AdV, adenovirus; hBoV, human bocavirus; hMPV,uman metapneumovirus.∗ Corresponding author at: Department of Virology, School of Public Health, Tehran University of Medical Sciences, Enghelab St,hods St, Poorsina Ave, P.O. Box 6446, Tehran 14155, Iran. Tel.: +98 21 88962343; fax: +98 21 88962343.
Prevalence of RSV circulating in Iran......................................................................127RSV gender differences ................................................................................... 129Regional differences in RSV...............................................................................129RSV co-infection .......................................................................................... 130Distribution of RSV genotypes.............................................................................130Geographical differences in RSV genotypes ............................................................... 131
Viral respiratory infections pose considerablehealth difficulties for people of various ages world-wide [1]. Respiratory syncytial virus (RSV) infectionis a leading cause of hospitalization in infants lessthan 1 year old and an important cause of clin-ical referral among children less than 5 years ofage in developed countries [2,3]; it is also consid-ered a significant pathogen in adults [1]. The majorviral respiratory pathogens include RSV, influenza(Flu) types A and B, parainfluenza (PIV) types 1—4,adenovirus (AdV), rhinovirus, enterovirus, humanbocavirus (hBoV) and human metapneumovirus(hMPV), all of which present with similar clinicalfeatures in infected patients [4]. RSV is a pneu-movirus belonging to the Paramyxoviridae family.This negative-sense single-stranded RNA virus ischaracterized by large syncytia in single-layercells [5]. Epidemiological studies have reportedthat RSV has a seasonal distribution pattern, withpeak prevalence between early November and late
infants. Recent studies describe the increased riskof wheezing and asthma after RSV bronchiolitis [6].
Increased risk of severe RSV infection hasbeen reported among premature infants; thosewith bronchopulmonary dysplasia, airway congen-ital abnormalities, cystic fibrosis, atopy, and Downsyndrome; and preterm children with chroniclung disease [1,7]. Considering the critical roleof the immune system, particularly neutrophils,in RSV infection, research has focused on itsimmunopathogenesis in order to characterize themolecular mechanisms of virus replication to designmore efficient drugs and vaccines [8—10].
Both classical and molecular diagnosis methodsare currently used for RSV detection; however,molecular assays, especially reverse transcriptionPCR (RT-PCR), offer increased sensitivity, speci-ficity, and rapidity [5]. The RSV genome encodes11 proteins, including two nonstructural proteins.The nucleotide sequence of the variable regionswithin the G glycoprotein are mainly used todetermine RSV genotype and for epidemiological
January in most communities [5]. RSV can beinvolved in upper and lower respiratory tract infec-tions and progress to bronchiolitis and pneumonia in
pcp
urposes [11]. Based on its reaction with mono-lonal antibodies against glycoprotein G and fusionrotein F, RSV has two main genetic subtypes,
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revalence of human respiratory syncytial virus circ
and B. There are 11 genotypes in subtype AGA1-7, SAA1, ON1, and NA1-2) and 20 in sub-ype B (GB1-4, BA1-10, SAB1-4, and URU1-2) [12].lthough these subtypes can co-circulate, sub-ype A tends to be predominant, which mighteflect time or geographical factors; virus circu-ation and evolution can be affected by severalther factors including virus infectivity and spon-aneous mutations as well as host group immunity13,14]. Gender-related susceptibility to RSV infec-ion, with male children reportedly more at riskhan females, remains controversial [12]; however,omparatively higher percentages of respiratorynfections are reported in women, which might beue to increased exposure to airborne infectionshrough frequent contact with children and elderlyamily members.
Since RSV plays a critical role in respiratorynfection epidemics and might be associated withsthma occurrence and development in later life15], RSV detection is of particular interest. Theulti-seasonal climate of Iran as well as its highlyopulated regions and diverse ethnic populationsrompted us to analyze published studies in ordero provide valuable information about the preva-ence of this virus in this population. Regional datas crucial for predicting the impact of RSV infec-ion on developing asthma and for improving virusiagnosis.
ethods
e reviewed all published studies about RSV in Irandentified by searching PubMed, Medline, nationalatabases (Scientific Information Database [SID],randoc, Iranmedex, MagIran), and related refer-nces from relevant articles. Search key wordsncluded ‘‘RSV’’, ‘‘respiratory syncytial virus,’’nd ‘‘Iran’’ in both English and Persian language.verlapping, unrelated, and unreliable data werexcluded. The following details were extractedrom each source: journal name, year of publica-ion, first author, season, number of cases, sampleize, age range (if available), city, number ofSV-positive individuals, patient clinical featuresif available), methods (direct immunofluorescencessay [IFA], indirect IFA, RT-PCR, real-time PCR,nzyme-linked immunosorbent assay [ELISA], ormmunochromatography), sample type (nasopha-yngeal swabs, nasopharyngeal aspirate, or throatwabs), hospitalization history (if available), and
ther respiratory viruses. Ten papers were iden-ified by ‘‘snowballing’’ (pursuing references ofeferences and electronic citation tracking), and7 papers by database browsing. A total of 21
Aaii
ing in Iran 127
eliable published studies were considered in theurrent review (Table 1). The data from these 21ross-sectional studies were both quantitative andualitative. A total of 4140 respiratory specimensnvestigated in 21 studies in Iran from 1996 to013 were included in our survey. These cases wereainly acute upper and lower respiratory infec-
ions. The age distribution of patients ranged from month to 60 years. Data were entered into aicrosoft Excel version 14 spreadsheet and descrip-
ive analyses conducted.
esult
revalence of RSV circulating in Iran
he age distribution of the 4140 cases was as fol-ows: in 14 of 21 studies, respiratory specimensere collected from children less than 5 years ofge; in 5 out of 21 studies, respiratory samples fromhildren less than 15 years of age were included inhe survey; the remaining studies collected samplesrom patients 5—60 years of age. Thus, the major-ty of samples were from children less than 5 yearsf age. Based on data analysis of 21 studies in Iran,75 of 4140, respiratory specimens were positiveor RSV. The average percentage of RSV positivity inll samples was 18.7% during 1996—2013 (Table 1).his pattern was consistent with estimated RSV
nfection prevalence of reported in epidemiologictudies in other countries. Molecular epidemiologyf circulating RSV detected in the Philippines [14]nd rural Thailand [16] revealed that 19% of casesospitalized with severe pneumonia were positiveor RSV. In the current study, the percentage of RSVositivity among respiratory samples from neigh-oring countries such as Pakistan was 17.8% amonghildren hospitalized for severe pneumonia dur-ng 2010—2011 [17]. A study conducted in Kenyaeported 16.5% of severe pneumonia cases wereSV-associated, consistent with our findings [18].he percentage of RSV positivity in Iran, however,as higher than in countries such as Cameroon
5.7%) [19] and Kenya (12.5%) [20], but lower thann recent reports from Latvia (33% to 57%) [21]nd Turkey (37.9%) [22]. The rate of RSV detec-ion varied over time in studies conducted in Iran,ith low and high rates of 5.7% and 45.8% reported
n 2007 and between 2009 and 2011, respectivelyTable 1). Despite the use of sensitive techniquesike RT-PCR, lower detection rates were reported in
rak and Ahwaz during 2008—2009 (Table 1); therere several possible reasons for this observation,ncluding hospitalization history, since all samplesn the Arak study were from outpatient cases. The
128
V. Salim
i et
al.
Table 1 RSV positivity rate from 21 studies of acute respiratory infection in Iran, n (%).
Location Year Age range No. ofcases
RSV positiverate
Type ofsampled
Methode Clinical features Hospitalization Ref.
Tehran Oct 1996 —Mar1998
<14 yr 268 33 (12.3%) NPS Cell cultureand DIF
Cough, bronchiolitis, fever Outpatient [40]
Tehran Nov—Mar 1998 <5 yr 365 70 (19.2%) NPA Cell cultureand DIF
Cough, coryza, pneumonia,bronchiolitis
14 (20%) [41]
Tehran Jan—May 1999 <5 yr 145 56 (38.6%) NPA DIF Bronchiolitis 36 (37.9%) [42]Tehran Mar—Nov 2001 2 m—14 yr 83 20 (23%) NPS IIF Cough, fever, rhinorrhea,
Prevalence of human respiratory syncytial virus circulating in Iran 129
Babo
l
2008
—20
10
<4
yr
180
40
(22.
2%)
Plas
ma
ELIS
A
Stri
dor,
tach
ypne
a,re
trac
tion
,
crac
kles
,w
heez
ing
40
(100
%)
[54]
Tehr
an
Sep
2009
—M
ar20
10<5
yr
96
44
(45.
8%)
NPA
RT-P
CR
Whe
ezin
g,
acut
ebr
onch
iolit
is,
asth
ma
bron
chio
litis
41
(43%
) [2
5]
Tehr
anN
ov
2009
—M
ar20
11<3
yr13
2
53
(40.
2%)
NPS
,
NPA
DIF
Feve
r,
coug
h,
cory
za,
bron
chia
l whi
zzin
g53
(100
%)
[55]
NIC
cN
ov
2007
—Ap
r20
13<2
yr48
5
94
(19.
4%)
TS
RT-P
CRAc
ute
resp
irat
ory
sym
ptom
s85
(90.
43%)
[13]
aTe
hran
,
Kara
j,
Gha
zvin
,
Isfa
han,
Shah
reza
,
Kerm
an,
Band
arab
bas.
bTe
hran
,
Vara
min
,
Kela
rdas
ht,
Isfa
han,
Sem
irom
,
Ham
edan
,
Zanj
an,
Alig
udar
z,
Shah
inde
j,
Khoy
,
Chal
dora
n,
Mia
ndoa
b,
Nag
hade
h.c
Nat
iona
l Infl
uenz
a
Cent
er
of
Iran
.d
Nas
opha
ryng
eal s
wab
s
(NPS
),
Nas
opha
ryng
eal a
spir
ate
(NPA
),
Thro
at
swab
s
(TS)
.e
Dir
ect
imm
unofl
uore
scen
ce
(DIF
),
indi
rect
imm
unofl
uore
scen
ce
(IIF
),
Reve
rse
tran
scri
ptio
n
poly
mer
ase
chai
n
reac
tion
(RT-
PCR)
, Re
al-t
ime
poly
mer
ase
chai
n
reac
tion
(Rt-
PCR)
,En
zym
e-lin
ked
imm
unos
orbe
nt
assa
y
(ELI
SA),
imm
onoc
hrom
atog
raph
y
(IM
C).
Ft
shaqttfmtRhsatt5bw
R
TorHtsn
R
OrtewrpTloc
igure 1 Distribution of respiratory syncytial virus infec-ions in Iran between 1996 and 2013, according to gender.
mall sample size in the Ahwaz study also mightave influenced the findings. High-quality samplesre required for good virus detection; lower sampleuality in these cities might also have contributedo the reduced detection rate of RSV. High detec-ion rates have been reported in a number of studiesrom Tehran (38.6%, 40.2%, and 45.8%) and Ker-an (37.5%) (Table 1), which were higher than
he 12.6—24.6% reported in other places (Table 1).SV infections were more frequently observed inospitalized patients (14 studies). Sixteen studiespecified the number of inpatients and outpatients,nd more than 63% of RSV-positive cases were hospi-alized. Our results using available studies indicatehat most RSV-positive outpatients were less than
years old. RSV infections were mainly observedefore 2 years of age [23]. No lethal RSV infectionsere reported in Iran from 1996 to 2013.
SV gender differences
he male-female ratio of RSV-positive patients inur analysis was 1.5:1, indicating a higher occur-ence of RSV infections in male patients (Fig. 1).owever, higher percentage of men enrolled inhe surveys might contribute to this finding, sincetudies from other countries have not reported sig-ificant gender differences [23].
egional differences in RSV
ur analysis revealed that available data on RSV-elated reports evaluated 19 of 31 provinces inhe center, northern, northwestern, and southwest-rn parts of Iran. No data were reported from theestern, eastern, northeastern, or southeastern
egions of Iran, except for Hormozgan and Kermanrovinces, which are located in the south (Fig. 2).
he reasons for variable geographic RSV preva-
ence cannot be concluded from available data, butne possible explanation might include the locallimates in these provinces [21]. It is apparent
130 V. Salimi et al.
viru geo
RdAtvdcrRshidw
iaf(
D
Figure 2 Geographic distribution of respiratory syncytialdistribution of respiratory syncytial virus cases related to
that additional data from all provinces in Iran arerequired to determine the exact prevalence pat-tern and frequency of RSV genotypes nationwide.Significant peaks of RSV prevalence were detectedin the cold seasons (November—March). This find-ing underlined the seasonal characteristics of RSVinfections in Iran, which is consistent with patternsof age and seasonal RSV prevalence reported inother studies [16,18].
RSV co-infection
Co-infection of RSV with other respiratory virusesis common, which may increase the risk of severeacute respiratory infections associated with respi-ratory distress, such as bronchiolitis, compared tosingle RSV infections [4]. RSV co-infection was onlyreported in two studies in our survey, consistingof 9/43(20.9%) [24] and 11/44 (20.5%) cases [25].According to Malekshahi et al. [24], the rate ofRSV co-infection with hMPV, PIV-1, AdV, and Fluwas 1/44 (2.32%), 4/44 (9.3%), 3/44 (6.97%), and
1/44 (2.32%), respectively. However, Chavoshzadehet al. [25] have shown that the RSV co-infection ratewith hMPV and rhinoviruses is 5/44 (11.36%) and4/44 (9.1%), respectively. No relationship between
Lipn
s cases between 1996 and 2013 (small stars) and genotypegraphical location in Iran, 2009—2013 (small triangles).
SV co-infections and increased severity of virus-ependent diseases was found in either study.ccording to the small number of reports on thisopic, the proportion of co-infections requireserification in future studies and evaluations toetermine if these findings are incidental or havelinical significance. Mixed infections have beeneported in many studies; however, the rates ofSV co-infection with other viruses have varied sub-tantially from 4% to 53% [26]. Hospitalized childrenad higher rates of co-infections [26], and RSV co-nfection with hMPV was reportedly associated withisease severity such that mechanical ventilationas required [17].In six of 21 studies, other respiratory viruses
ncluding AdV, PIV types 1—3, hBoV, Flu type And B, and hMPV were also detected independentlyrom RSV infections; AdV (14.22%) and PIV type 310.15%) were most commonly observed (Table 2).
istribution of RSV genotypes
imited information exists regarding RSV genotypesn Iran. Among the current studies, only threerovided information about RSV genotypes usingested RT-PCR and partial G protein sequencing.
Prevalence of human respiratory syncytial virus circulating in Iran 131
Table 2 Detection rates of RSV, adenovirus, influenza virus, parainfluenza virus, boca virus and metapneumovirusin children with acute respiratory infection in 21 studies in Iran between 1996 and 2013.
type 3404 41 (10.15%) 2 2001—2002, 2009—2010 [45,52]
Human bocavirus 261 21 (8.02%) 1 2003—2004 [46]Parainfluenza virus
type 2202 13 (6.43%) 1 2001—2002 [52]
Influenza virus type A 1125 59 (5.24%) 5 2001—2004, 2007—2009 [40,45—47,52]Parainfluenza virus
type 1904 42 (4.65%) 4 2001—2002, 2007—2009 [28,45,47,52,28]
Influenza virus type B 404 8 (1.98%) 2 2001—2002, 2008—2009 [45,52]Human
metapneumovirus202 1 (0.5%) 1 2008—2009 [45]
We just considered the studies that have detected RSV as well as other respiratory viruses. We have excluded those studies that
TrtBttgiaGptCiwnogeidtBys
G
Tiicir
eItteGRfvTpdct
(tidlthiatpbsfp
detected other respiratory viruses except RSV.
he first report, from Faghiloo et al. (2011),eported a prevalence of GA1, GA2, and GA5 duringhe winter in 2007—2008 [27], and GA1, GA2, andA during the same season in 2009 [28]. In 2014,he same group identified GA1, GA2, and BA geno-ypes from 2009 to 2013 [13]. The circulating RSVenotypes in Iran fluctuated in 2007—2013. Accord-ngly, GA2 was predominant during 2007—2008nd reappeared during 2010—2012. Both GA1 andA2 circulated in 2011—2013; however, GA1 wasredominant. GA5 was only detected in 2008. Geno-ype BA with a 60-nucleotide duplication in the-terminal region of the G protein was detected
n 2009 and 2013. These findings were consistentith other studies reporting shifts in the predomi-ant genotype between seasons [29]. The interplayf pre-existing immunity in the community and theenetic and antigenic properties of the RSV virus tovade the immune response may explain changesn genotype dominance over time [30]. The pre-ominance of RSV-A viruses has been attributedo increased variability among RSV-A strains [30].ased on the fact that the dominant strains shiftearly, evasion of immunity induced by previoustrains may be a mechanism for re-infection [31].
eographical differences in RSV genotypes
he geographical distribution of RSV genotypesn Iran also varied: genotype GA2 was predom-
nant in the south; GA1, GA2 and BA in theenter; and GA1 in the north (Fig. 2). Monitor-ng circulating RSV strains in different geographicalegions is essential, particularly in the western,
raAM
astern, northwestern, and southeastern parts ofran, where available data is lacking. The con-inuous circulation of genotype GA2 emphasizeshe stability of this subtype; it has become anpidemic in Europe, Asia and Africa [30,32,33].enotypes GA2 and BA are also the most commonSV genotypes worldwide [30,32,34]. Recent datarom Israel indicated that the majority of RSV-Airuses detected during 2008—2012 was GA2 [32].hese data also suggest that GA2 has been theredominant RSV-A genotype circulating in the Mid-le East between 2006 and 2012 [32]. Howeveronflicting data exist on whether RSV evolution isemporally or geographically related [30,32].
As indicated in Fig. 2, RSV virus subgroups AGA1, GA2, and GA5) and B (BA) co-circulate inhe same area with various patterns of predom-nance during epidemic periods. Recent studiesemonstrating the predominance of genotype BA ateast in subtype B may suggest a selective advan-age for this genotype; however, the mechanismas not yet been defined [35]. Genetic changesn the BA genotype have been proposed to confer
neutralization-resistance phenotype that allowshese strains to escape previous host immunity androvide an opportunity for increased transmissi-ility in susceptible populations [35]. An annualhift of dominant strains may explain frequent rein-ections due to evasion of immunity induced byrevious strains [21]. Several attempts to clarify the
elationship between clinical severity of infectionnd RSV subgroups have postulated that subgroup
is associated with more severe disease [34,36].artinello et al. [36] reported that genotype GA3
132 V. Salimi et al.
n thiunos
sr(((mqaRs
rsar(sRdthFheme
nma
Figure 3 Overview of methods used in studies included ipolymerase chain reaction (RT-PCR), enzyme-linked imm
might be associated with more severe disease. Theyclaimed that amino acid variations in the third C-terminal hypervariable region of the RSV G genemight be responsible for the severity of RSV infec-tions, such as bronchiolitis [34,36]. However, somereports have concluded that the severity of RSV-related disease was not related to subgroups orgenotypes but was instead associated with viralload during primary RSV infection [34]. It is notknown to what extent these inconsistencies mightbe attributed to differences in the definitions ofdisease severity, RSV subgroup distribution, studydesign, or study populations [5].
Discussion
RSV is responsible for approximately 3.4 millionhospitalizations associated with lower respiratorytract infections and almost 200,000 deaths amongchildren less than 5 years of age [37]. Of thesedeaths, 99% occur in developing countries [37].The current review of 21 published studies fromvarious geographical regions in Iran allowed usto estimate the percentage of respiratory tractinfections caused by RSV infection as well as thedistribution of RSV genotypes in Iran. Our analy-sis revealed an overall percentage RSV positivityrate of 18.7% during 1996—2013. The sensitiv-ity of the assays used in various studies may be
variable [38]. Jansen et al. [39] described a signif-icant efficiency of nasal swabs compared to throatswabs for RSV detection among different sampletypes. The sample types collected from patients in
lvi[
s review. Immunofluorescence (IF), reverse transcriptionorbent assay (ELISA), immunochromatography (IMC).
tudies included in our survey included nasopha-yngeal swabs (42.8%), nasopharyngeal aspirate14.3%), both nasopharyngeal swabs and aspirates9.5%), throat swabs (19%), serum (4.8%), plasma4.8%); 4.8% of studies did not provide this infor-ation (Table 1) [13,24,25,27,28,40—55]. Conse-uently, proper sampling and standard techniquesre highly recommended to avoid underestimatingSV-associated disease burden due to low-qualitypecimens [31].
Several reasons could explain the controversyegarding RSV infection rates. First, the low sen-itivity of conventional virus detection tests suchs immunochromatography, ELISA, and immunofluo-escence assays, were exploited in several studiesTable 1; Fig. 3). These methods are 12—50% lessensitive than PCR-based methods [3,38]. Second,SV might have been cleared prior to sampling andelayed sampling may lead to underestimation ofhe true viral infection rate. Third, viral RNA mayave degraded during storage in hospital freezers.inally, differences in study design, sample types,ospitalization period, and patient age might influ-nce study outcomes. However, these discrepanciesight also reflect real regional and temporal differ-
ificant genetic variation in circulating strainsay involve different pathogenicity and virulence
mong patients with RSV infections. Several pub-
ications have recently documented that novelariants may have enhanced clinical severity withncreased replication in the lower respiratory tract34,36]. However, our findings do not support these
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ebavspawRPicptit(eto[
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revalence of human respiratory syncytial virus circ
bservations. Emerging RSV variants with a selec-ive advantage due to increased genetic diversityay confer low cross-protection by pre-existing
ntibodies to RSV strains previously circulatingn Iran. Multiple genotypes co-circulated during007—2013. The co-circulation of multiple geno-ypes in some regions of Iran might be associatedith the outbreak of RSV among children with fevernd respiratory symptoms in the epidemic seasonFig. 2).
Because there are few studies on the molecularpidemiology of RSV in Iran, a larger population-ased study is required to further delineate thessociation of clinical severity of infection withirus genotype in different areas. Better under-tanding of the molecular epidemiology of RSV willrove instrumental in developing efficient vaccinesnd antiviral pharmacotherapy [8,9,35]. Thereere several limitations in our study, including: (1)SV viral load was not measured by quantitativeCR; viral load may have been associated with co-nfection or disease severity. (2) Most studies wereonducted in a single hospital or city; however,atterns of RSV genotype frequency and distribu-ion may vary with location. (3) Not all regionsn Iran were studied or surveyed for RSV geno-ypes, and additional RSV genotypes are possible.4) No data were available on the timing of dis-ase onset. Despite these limitations, our study ishe first and complete review on RSV epidemiol-gy in Iran covering research over the last 17 years13,24,25,27,28,40—55].
Although deaths associated with RSV have beenare in the last two decades [3], and no reportedethal RSV infections were reported in Iran, theSV mortality rate may not be zero. Clinicianshould consider that children suffering from com-lex chronic conditions [6] and genetic disorders [7]re significantly more prone to death from severeSV infections. Therefore, more comprehensiveopulation-based studies on pediatric infectiousiseases are required to determine the risk factorsf severe RSV infections in Iran.
In conclusion, this review highlights the neces-ity of a standard molecular surveillance programn Iran. Future investigations of different areas ofran, particularly regions with a paucity of data,re needed in order to determine RSV prevalencend genotype distribution nationwide. ImprovingSV surveillance would allow timely understandingf the epidemiological, clinical, and pathologi-al characteristics of novel RSV genotypes. Since
igh-risk populations are at increased risk of RSVnfection and there is no data about passive immu-ization against RSV in Iran, this information willssist policy makers in determining which regions
ing in Iran 133
nd sub-populations will most benefit from RSV pro-hylaxis and treatment.
uthors’ contributions
S and MTY participated in the study design anderformed statistical analysis. VS and STY con-eived of the study. JY, LB, and TMA wrote theanuscript. All authors read and approved the finalanuscript.
unding
o funding sources.
ompeting interests
he authors declare that they have no competingnterests.
thical approval
ot required.
cknowledgement
e thank Dr. Seyed Alireza Nadji for critical com-ents on the manuscript.
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