studies from the united states , europe and hong kong indicate that young children are at risk for serious illness and hospitalization from influenza virus infection . 

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  in the united states , 80% of influenzaassociated hospitalization in children occurs in those < 5  years of age and more than half of influenza mortality among children occurs in this age group . 

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  between 1996 and 2005 , the thailand ministry of public health passive surveillance system reported between 21  176 and 55  559 cases of clinically diagnosed influenza ( inpatient and outpatient ) annually for an incidence of between 34 and 87 cases per 100  000 population . 
  between 1999 and 2002 ,
the national influenza surveillance system reported an average annual agespecific incidence rate in children aged 04  years were only 42 per 100  000 population . 
 
this figure may underestimate the true burden since influenza often presents with nonspecific respiratory tract symptoms in young children and laboratory confirmation of influenza is not routinely performed in thailand . in 2001 ,
virological influenza surveillance conducted in outpatient clinics in thailand identified influenza virus in cell culture in 341 ( 48% ) of 711 respiratory specimens tested .
sixty percent of these specimens were from children . 
  in 2004 , a large study in rural eastern thailand found that 11% of hospitalized pneumonia and 23% of influenzalike illness ( ili ) managed in the outpatient department was the result of influenza virus infection .
this populationbased study included comprehensive laboratory confirmation and reported that young children and the elderly were most affected by influenza .
the researchers estimated an incidence of 1420 influenza infections per 100  000 outpatients , a burden 43 times greater than that recorded by the national passive surveillance system during the same period . 
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when compared to the age distribution of the population , the proportion of patients with laboratory confirmed influenza pneumonia who were < 1  year of age was 6.2 times higher than expected . 

 
influenza infection is characterized by nonspecific symptoms that can make it difficult to distinguish from febrile respiratory illness caused by other pathogens . 
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in thailand , the use of rapid diagnostic tests for influenza are increasing and have been shown to be useful for surveillance and to guide clinical decision making . 

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  studies from the united states have demonstrated a high burden of serious complications of influenza in otherwise healthy children which lead to a 2004 us advisory committee on immunization practices ( acip ) recommendation that healthy children aged 623  months receive influenza vaccine annually . 
  in 2006 ,
the acip extended the recommendation for annual influenza vaccination to all children aged 659  months . 
 
a limited but growing body of evidence suggests that influenza is also an important cause of illness in tropical countries , but more data are needed especially in toddlers and infants . 
 
we studied influenzaassociated pediatric hospital admissions , the clinical manifestations of influenza , and the performance of rapid diagnostic tests for influenza a in children < 5  years of age at queen sirikit national institute of child health , a tertiarycare , hospital for children in bangkok , thailand .
we conducted a prospective study of hospitalized children aged 05  years at queen sirikit national institute of child health during july 5 , 2004 to july 3 , 2005 .
patients with a diagnosis of lower respiratory tract infections including ; viral croup , bronchitis , bronchiolitis and pneumonia were enrolled .
in addition , patients with ili per the who case definition with fever > 38c and cough or sore throat in the absence of other known causes ( e.g. , urinary tract infections , dengue fever etc ) . patients reporting an onset of symptoms more than 5  days before admission were excluded . the study was explained to caregivers and written informed consent was obtained .
we then obtained a medical history , conducted a physical examination and collected respiratory swab specimens .
all patients were tested using one of two rapid influenza diagnostic tests and also influenza viral culture upon admission .
other medical investigations and treatments were provided by attending physicians according to the routine standard of care .
these tests detect influenza type a and yield results in 1530  min , but are not able to detect influenza type b. nasal swabs were collected with plain cotton swab for both rapid tests .
nasopharyngeal swabs for influenza virus isolation were collected with dacron swab and placed in viral transport media composed of nacl 1  gm , k2hpo4 1  gm , beef extract 1  gm , peptone 3  gm , add dw2 up to 200  ml , add antibiotics to make final concentration as follow ; penicillin 1000 unit / ml , streptomycin 1000  g / ml , fungizone 5  g / ml and ph was adjusted to 7.0    0.2 with 1  n naoh , vtm then transported chill to the thai national influenza center , national institute of health , ministry of public health for influenza virus isolation .
the specimens were cultured using madin darby canine kidney ( mdck ) cells and observed for cytopathic effect .
isolated viruses were confirmed as influenza and typed by reference antisera for influenza a or b with immunofluorescent staining technique .
patients with a positive rapid test were treated with oseltamivir ( tamiflu ) according to the recommended doses per kilogram .
because tissue cell culture is considered the gold standard diagnostic method , only children with a positive viral culture were included in this analysis .
clinical findings of influenza and noninfluenza patients were compared using chisquare test and considered significant at p  <  0.05 .
sixtythree percent of patients were enrolled on day 4 or 5 after the onset of the illness ( table  1 ) . 
characteristics of the enrolled patients influenza viruses were isolated in 39 patients ( 8.6% ) .
thirtyfour of them were influenza a ( 87.2% ) and five of them were influenza b ( 12.8% ) .
most of the influenza b viruses were isolated during december 2004 to february 2005 ( fig
influenza activity demonstrated seasonal variation with two peaks during august to october and january to april .
the highest monthly proportion of influenza positive patients was in february ( 16.7% ) ( fig .  1 ) . 
influenza infection by months . among 39 cases of cultureconfirmed influenza , the mean age of influenza
thirtyone patients ( 79.5% ) were previously healthy while others had underlying diseases , including asthma or hyperactive airway diseases 4 ( 10.3% ) , cerebral palsy 1 ( 2.6% ) , ventricular septal defect 1 ( 2.6% ) , adrenogenital syndrome 1 ( 2.6% ) and sotos syndrome 1 ( 2.6% ) .
38.5c ) , cough , constitutional symptoms ( anorexia , irritability , and lethargy ) , rhinorrhea , myalgia , vomiting , respiratory distress , abnormal chest auscultations ( wheezing , rale , and stridor ) , injected pharynx , diarrhea , conjunctival injection , and seizure .
temperature > 38.6c , conjunctival injection and stridor were significantly higher in influenza patients ( p  <  0.05 ) while respiratory distress and rale were significantly higher in noninfluenza patients ( p  <  0.05 ) .
seizures were presented in 10.3% of influenza patients and 7.4% of noninfluenza patients ( table  2 ) . 
n  =  32 ( only in evaluable older children ) ; * p  <  0.05 .
there were seven children with influenza were positive by rapid test but not the viral culture .
the mean age of these patients was 14  months compared to 20  months in cultureconfirmed patients . among the seven patients , clinical features were high fever ( t  >  38.5c ) ( 100% ) , cough ( 100% ) , constitutional symptoms ( anorexia , irritability , and lethargy ) ( 100% ) , rhinorrhea ( 86% ) , vomiting ( 71% ) , respiratory distress ( 43% ) , and seizure ( 14% ) .
the features were similar to cultureconfirmed patients except the fever ; all seven patients had high fever ( t  >  38.5c ) while in cultureconfirmed influenza the majority ( 59% ) had high fever and the rest had lowgrade or no fever ( table  2 ) .
the clinical diagnosis on admission for these children with cultureconfirmed influenza included lower respiratory tract infection ( pneumonia , bronchitis , bronchiolitis , and viral croup ) , upper respiratory tract infection ( rhinopharyngitis and pharyngitis ) , influenza , viral myositis , and gastroenteritis ( table  3 ) . 
clinical diagnosis on admission among 39 influenza patients , 20 ( 51% ) required oxygen therapy .
two patients needed mechanical ventilation ; one case was previously healthy and the other had underlying sotos syndrome with recurrent pneumonia .
the length of the hospital stay was 124  days , the highest percentage was between 610  days ( 23.1% ) and 48.8% required hospital stays of 5  days or longer ( table  4 ) . 
length of hospital stay rapid tests for influenza a was evaluated compared to viral tissue cell culture .
directigen flu a was tested in 394 patients and now flu a was tested in 62 patients ( according to changes in the test supplied by the department of communicable diseases control ) .
the sensitivity of directigen flu a was 50% and specificity was 98% while now flu a had sensitivity 33% and specificity 98% ( 5 , 6 ) . 
sensitivity and specificity of directigen flu a 
  sensitivity and specificity of now flu a 
  * positive viral cultures for influenza a but not influenza b ( 34 from 39 totals ) were used to evaluate sensitivity and specificity of the rapid tests , since the tests specified for influenza a diagnosis .
directigen flu a was tested in 394 patients and now flu a was tested in 62 patients ( according to changes in the test supplied by the department of communicable diseases control ) .
the sensitivity of directigen flu a was 50% and specificity was 98% while now flu a had sensitivity 33% and specificity 98% ( 5 , 6 ) . 
sensitivity and specificity of directigen flu a 
  sensitivity and specificity of now flu a 
  * positive viral cultures for influenza a but not influenza b ( 34 from 39 totals ) were used to evaluate sensitivity and specificity of the rapid tests , since the tests specified for influenza a diagnosis .
during 20042005 , 9% of children 5years old that were hospitalized with lower respiratory tract infection or ili were culturepositive for influenza virus infection . because our study did not use the more sensitive rtpcr or serological laboratory diagnostic methods ,
influenza was isolated throughout the year round and peak activities occurred during june to october and january to march , a finding that was consistent with published reports . 
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  of interest , peak influenza activity in thailand usually follows the beginning of school year in the middle of may each year .
school aged children are believed to play a major role in the propagation of seasonal influenza epidemics . 
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  the clinical manifestations of influenza infection in our study are similar to those previously described . 
 
fever , cough , rhinorrhea , and constitutional symptoms are the most common presenting symptoms .
influenza in young children was significantly associated with highgrade fever ( temperature > 38.6c ) . and we found unusual diagnoses included viral myositis and gastroenteritis which shows that in young children influenza virus infection may not present with respiratory tract infection . in our study , seizures were presented in four ( 10.3% ) of influenza patients probably due to highgrade fevers .
neurological manifestations of influenza virus infection , including febrile seizures , encephalitis , and meningitis have been reported and warrant further study in thai children . 
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while the rapid test is proved very useful to identify influenza patients to conduct research and guide treatment decisions , the sensitivity of the tests was less than that reported elsewhere . 
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  the sensitivity of now flu a test and directigen flu a were only 33% and 50% , respectively .
these markedly low figures were probably due to two reasons ; first , most of the patients in our study were enrolled at the 4th or 5th day of illness , a time when influenza viral antigen may no longer be present in the nasopharynx in sufficient quantities to yield a positive rapid test .
second , we used of a nasal swab specimen rather than a nasal wash , a nasopharyngeal aspirate or a nasopharyngeal swab specimen that is recommended by the manufacturers .
this finding underscores the importance of proper training and supervision of clinical staff who use rapid influenza diagnostic tests . 

  in conclusion
, our study demonstrates that influenza virus infection is an important cause of hospitalization in healthy thai children < 5  years of age .
clinical characteristics of influenza in young children are highgrade fever , cough , constitutional symptoms , rhinorhea , and abnormal breath sounds . especially during the months of july to october and january to march when influenza activity appears to be highest , influenza infection should be considered in the differential diagnosis when caring for patients with acute upper or lower febrile respiratory infection .
rapid tests for influenza a had a moderate sensitivity and high specificity that can help guide clinical treatment and the wider application of these tests in thailand should be considered .
further research on influenza infection in thai children using rtpcr , serology , and tissue cell culture laboratory diagnostic method is needed to improve clinical care , inform vaccine introduction decisions , and to develop improved practices for nonpharmaceutical interventions to control seasonal epidemics .
 
 background   studies in north america and europe have shown that young children are at increased risk of serious complications and hospitalization from influenza infection . in thailand , however , influenza is commonly considered a mild infection that rarely requires hospitalization . 
 an improved understanding of the burden of serious complications from influenza infection in young children is needed to inform clinical treatment and vaccination guidelines . 
 
 methods   we conducted a prospective study of children 05  years of age with lower respiratory tract infection or influenzalike illness admitted to a pediatric tertiarycare hospital in bangkok , thailand during july 2004 to july 2005 . 
 all respiratory specimens were tested for influenza using a rapid antigen test and tissue cell culture . 
 
 results   thirtynine of 456 ( 8.6% ) hospitalized children had culturepositive influenza . 
 eighty percent of hospitalized influenza patients had no underlying chronic illnesses . 
 nineteen ( 49% ) influenza patients required hospital stays of 5  days or more and two patients required mechanical ventilation . 
 influenza activity demonstrated bimodal seasonal variation with peak activity from august to october and january to april . 
 cough was present in 38 ( 97% ) cases and fever > 38.5c was significantly associated with influenza . 
 
 conclusion   influenza is an important cause of hospitalization in children < 5  years of age in thailand . 
 children < 5  years should be considered as a target group when establishing clinical guidelines for antiviral treatment and influenza vaccination . 
Introduction
Materials and methods
Results
Performance of the rapid diagnostic test for influenza A
Discussion