the novel influenza a ( h1n1 ) virus was first detected in mexico during april 2009 , and then in united states ( us ) . the scientists call this a  quadruple reassortant  virus and hence this new ( novel ) virus is christened  influenza a ( h1n1 ) virus  . the world health organization ( who ) raised the pandemic level from 5 to 6 , the highest level , after the documentation of human to human transmission of the virus in at least three countries in two of the six world regions defined by the who . india reported first confirmed case of influenza a ( h1n1 ) during may , 2009 . saurashtra region is the western part of gujarat state , reported first case in august 2009 . although many individuals presented with mild , self - limited illness , no signs of pulmonary involvement ; some people required intensive care and received maximal life support measures . the objective of present study was to identify characteristics associated with severity of disease in 511 confirmed cases of pandemic h1n1 influenza , hospitalized in various hospitals of rajkot . total 511 patients found positive for pandemic influenza a ( h1n1 ) and admitted in different hospitals of rajkot from september 1 , 2009 to january 31 , 2011 combining two waves , were included for analysis . though no cases were reported after november 2010 , the surveillance was continued till february 2011 . ministry of health and family welfare ( mohfw ) , government of india ( goi ) had issued guidelines for categorization of influenza a ( h1n1 ) cases during screening for home isolation , testing treatment , and hospitalization [ table 1 ] . current report describes total 511 patients belonging to category c who were tested and confirmed , hospitalized , monitored , and included in the analysis . categorization of influenza a ( h1n1 ) patients as per clinical features all patients were categorized as : ( 1 ) cases as severe influenza a ( h1n1 ) patients - those patients needed intensive care unit ( icu ) or died . patients with one or more of following feature were admitted in icu : ( a ) spo2 < 60 mm hg , ( b ) not maintaining spo2 with oxygen mask , ( c ) tachypnea and dyspnea , ( d ) respiratory rate > 40/min , ( e ) with altered sensorium , ( f ) patchy consolidation on x ray chest . ( 2 ) controls as non - severe influenza a ( h1n1 ) patients  those admitted in wards survived and not needed intensive care . patients not fulfilling any of above criteria were admitted in wards for clinical management . for patients below 15 years of age following criteria were used to categorize as severe influenza a ( h1n1 ) patients pao2 < 60 mm of hg , hypercapnoea ( pco2 > 55 mm of hg , severe metabolic acidosis ( ph < 7.2 ) , severe respiratory distress ( respiratory rate > 70/min ) , severe lower chest wall indrawing , altered sensorium , grasping or apnea , and shock . several types of data was collected from the patients : date and time of admission to hospital / icu , age , sex , residential status , co - existing conditions , date , and time of first symptoms . also , as mentioned , data for other variables were collected [ table 2 ] . baseline characteristics of 2009 influenza a ( h1n1 ) infected patients in saurashtra region from september 2009 to january 2011 all patients admission history and their medical records were assessed from swine flu ward for initial clinico - epidemiological details , and from medical record and statistics department after patient discharge / death from various hospitals of rajkot city . line list number was given to every patient to avoid duplication at any time during study period . approval by institutional review board was not required because the present infectious disease was covered under epidemic act and the state health department has implemented the epidemic disease control act , 1897 . the influenza a ( h1n1 ) virus was detected with the use of real time reverse transcriptase polymerase chain reaction ( rt - pcr ) assay by collecting two swabs from naso - pharynx and one from pharynx , in accordance with the protocol from the us centers for disease control and prevention , as recommended by the who . all data was entered in ms excel , and analyzed by using epi info software ( version 3.5.1 ) from cdc . variables that showed p < 0.20 in bivariate analysis were selected for logistic regression to examine the relation between variables of interest and severity of disease . results from logistic regression analyses expressed as odds ratio ( or ) , and 95% confidence intervals ( cis ) . the p values and cis reported here reflect a two tailed  level of 0.05 . total 511 patients found positive for pandemic influenza a ( h1n1 ) and admitted in different hospitals of rajkot from september 1 , 2009 to january 31 , 2011 combining two waves , were included for analysis . though no cases were reported after november 2010 , the surveillance was continued till february 2011 . ministry of health and family welfare ( mohfw ) , government of india ( goi ) had issued guidelines for categorization of influenza a ( h1n1 ) cases during screening for home isolation , testing treatment , and hospitalization [ table 1 ] . current report describes total 511 patients belonging to category c who were tested and confirmed , hospitalized , monitored , and included in the analysis . all patients were categorized as : ( 1 ) cases as severe influenza a ( h1n1 ) patients - those patients needed intensive care unit ( icu ) or died . patients with one or more of following feature were admitted in icu : ( a ) spo2 < 60 mm hg , ( b ) not maintaining spo2 with oxygen mask , ( c ) tachypnea and dyspnea , ( d ) respiratory rate > 40/min , ( e ) with altered sensorium , ( f ) patchy consolidation on x ray chest . ( 2 ) controls as non - severe influenza a ( h1n1 ) patients  those admitted in wards survived and not needed intensive care . patients not fulfilling any of above criteria were admitted in wards for clinical management . for patients below 15 years of age following criteria were used to categorize as severe influenza a ( h1n1 ) patients pao2 < 60 mm of hg , hypercapnoea ( pco2 > 55 mm of hg , severe metabolic acidosis ( ph < 7.2 ) , severe respiratory distress ( respiratory rate > 70/min ) , severe lower chest wall indrawing , altered sensorium , grasping or apnea , and shock . several types of data was collected from the patients : date and time of admission to hospital / icu , age , sex , residential status , co - existing conditions , date , and time of first symptoms . also , as mentioned , data for other variables were collected [ table 2 ] . baseline characteristics of 2009 influenza a ( h1n1 ) infected patients in saurashtra region from september 2009 to january 2011 all patients admission history and their medical records were assessed from swine flu ward for initial clinico - epidemiological details , and from medical record and statistics department after patient discharge / death from various hospitals of rajkot city . line list number was given to every patient to avoid duplication at any time during study period . approval by institutional review board was not required because the present infectious disease was covered under epidemic act and the state health department has implemented the epidemic disease control act , 1897 . the influenza a ( h1n1 ) virus was detected with the use of real time reverse transcriptase polymerase chain reaction ( rt - pcr ) assay by collecting two swabs from naso - pharynx and one from pharynx , in accordance with the protocol from the us centers for disease control and prevention , as recommended by the who . all data was entered in ms excel , and analyzed by using epi info software ( version 3.5.1 ) from cdc . variables that showed p < 0.20 in bivariate analysis were selected for logistic regression to examine the relation between variables of interest and severity of disease . results from logistic regression analyses expressed as odds ratio ( or ) , and 95% confidence intervals ( cis ) . the p values and cis reported here reflect a two tailed  level of 0.05 . out of 511 cases of influenza a ( h1n1 ) , 140 patients ( 27.4% ) reported with severe disease and 371 patients ( 72.6% ) as non - severe disease [ table 2 ] . among 140 severe disease patients , mortality was reported in majority ( 90.7% ) patients , while only 9.3% patients needed intensive care and survived . month - wise distribution of influenza a ( h1n1 ) infected patients for two waves is shown in figure 1 . month wise distribution of infected influenza a ( h1n1 ) cases from september 2009 to january 2011 in saurashtra region the median age of 30 years was reported in both severe ( range 4 months to 68 years ) and non - severe disease patients ( range 1 month to 70 years ) . more females ( 60.7% ; or = 0.53 , ci = 0.36 - 0.79 ) needed intensive care than males . total 47 ( 31.3% ) cases had an underlying medical condition [ table 3 ] , reported more among severe disease patients ( 33.6% ) . diabetes mellitus ( dm ) ( 10.2% ) and/or hypertension ( 11.9% ) was mainly reported underlying condition among non - severe disease . < 0.05 ) was reported mainly among patients with severe disease [ table 3 ] . among reported female patients , 14 were pregnant with a range of 4 to 9 months of amenorrhea , a significant risk of severe disease was reported with pregnancy ( or = 0.19 , ci = 0.08 - 0.48 ) . pneumonia was reported more among patients with severe disease ( 86.7% ; or = 0.30 , ci = 0.16 - 0.53 ) [ table 5 ] . clinical features and coexisting conditions among influenza a ( h1n1 ) infected patients laboratory and radiological findings of influenza a ( h1n1 ) infected patients correlates of disease severity among severe ( n=140 ) and non - severe ( n=371 ) influenza a ( h1n1 ) patients more than half of the patients with severe disease , that is , 58.6% and 44.5% non - severe disease patients were first treated by general practitioner / physician and then referred to a higher centre ( or = 0.56 , ci = 0.38 - 0.83 ) . among 140 severe disease patients who needed intensive care , 90.7% reported mortality and 9.3% survived . out of 140 severe disease patients , 27.1% received antiviral drug within 2 days of onset of illness . median time of 3 days for ventilator support , more than 5 days hospitalization ( p < 0.05 ) , and antiviral drug administration ( p < 0.05 ) has been reported among severe disease patients . out of 511 cases of influenza a ( h1n1 ) , 140 patients ( 27.4% ) reported with severe disease and 371 patients ( 72.6% ) as non - severe disease [ table 2 ] . among 140 severe disease patients , mortality was reported in majority ( 90.7% ) patients , while only 9.3% patients needed intensive care and survived . month - wise distribution of influenza a ( h1n1 ) infected patients for two waves is shown in figure 1 . month wise distribution of infected influenza a ( h1n1 ) cases from september 2009 to january 2011 in saurashtra region the median age of 30 years was reported in both severe ( range 4 months to 68 years ) and non - severe disease patients ( range 1 month to 70 years ) . more females ( 60.7% ; or = 0.53 , ci = 0.36 - 0.79 ) needed intensive care than males . total 47 ( 31.3% ) cases had an underlying medical condition [ table 3 ] , reported more among severe disease patients ( 33.6% ) . diabetes mellitus ( dm ) ( 10.2% ) and/or hypertension ( 11.9% ) was mainly reported underlying condition among non - severe disease . < 0.05 ) was reported mainly among patients with severe disease [ table 3 ] . among reported female patients , 14 were pregnant with a range of 4 to 9 months of amenorrhea , a significant risk of severe disease was reported with pregnancy ( or = 0.19 , ci = 0.08 - 0.48 ) . pneumonia was reported more among patients with severe disease ( 86.7% ; or = 0.30 , ci = 0.16 - 0.53 ) [ table 5 ] . clinical features and coexisting conditions among influenza a ( h1n1 ) infected patients laboratory and radiological findings of influenza a ( h1n1 ) infected patients correlates of disease severity among severe ( n=140 ) and non - severe ( n=371 ) influenza a ( h1n1 ) patients more than half of the patients with severe disease , that is , 58.6% and 44.5% non - severe disease patients were first treated by general practitioner / physician and then referred to a higher centre ( or = 0.56 , ci = 0.38 - 0.83 ) . among 140 severe disease patients who needed intensive care , 90.7% reported mortality and 9.3% survived . out of 140 severe disease patients , 27.1% received antiviral drug within 2 days of onset of illness . median time of 3 days for ventilator support , more than 5 days hospitalization ( p < 0.05 ) , and antiviral drug administration ( p < 0.05 ) has been reported among severe disease patients . present study mentions severe influenza a ( h1n1 ) virus infection in residents of saurashtra region . a total of 511 patients reported confirmed and were hospitalized during the study period , and categorized as patients having severe ( n = 140 ) and non - severe disease ( n = 371 ) . patients with severe diseases reported median age of 30 years which is higher than that of portugal ( 23 ) and south korea ( 11 ) , but lower than that was observed in a study from canada ( 37 ) . two - third patients with severe disease were above the age group of 25 years in which 60.7% were females . it indicates that adults and females ( or = 0.53 , ci = 0.36 - 0.79 ) appear to be at higher risk of death due to pandemic influenza a ( h1n1 ) virus infection compared to children or teenagers . more cases of severe influenza were reported from the urban area ( or = 1.68 , ci = 1.13 - 2.49 ) than rural area . this may be because of dense population in urban area favors spread of virus infection . among all the patients , a median time of 5 days was reported from onset of illness to diagnosis of influenza a ( h1n1 ) . more than half ( 58.6% ) of the patients with severe disease were treated first at general practitioner / physician ( or = 0.56 , ci = 0.38 - 0.83 ) and then referred to a higher center . the time duration between onset of illness and hospital admission and diagnosis was more than other countries . the possible justification is that patients seek treatment at local level from general practitioners and physicians , but with no or little improvement after initial treatment , they were referred to a higher center for further investigation and management . present study reported median time of 4 days for hospital stay among severe disease patients ( or = 0.24 , ci = 0.16 - 0.37 ) with 65.7% patients having less than 5 days of hospital stay ; compared to 7 days median time and 32.4% non - severe disease patients . it also indirectly reflects that patients with more severe disease with delayed referral , reaches to higher center at critical stage . current interim cdc guidelines for pandemic and seasonal influenza recommended the use of either oseltamivir or zanamivir for hospitalized patients . indian government authorities have recommended and supplied oseltamivir to the state governments for distribution in tertiary care centers and district . in the present study area , all the influenza a ( h1n1 ) infected fatal cases received oseltamivir after hospital admission . however , only 27.1% severe disease patients received it within 2 days of onset of illness which when compared was higher in china ( 12.8% ) , but lower than in united states ( 38 - 50% ) . initial primary treatment at general practitioners or local physician level and delayed referral to higher center and investigation , may be a possible explanation for delayed start of oseltamivir in suspected or confirmed influenza a ( h1n1 ) patients . when started early , antiviral drug has beneficial effect . study reported that patients admitted to icu or died were less likely to receive such therapy within 48 hours after onset of symptoms . after complete course of oseltamivir therapy ( or = 0.38 , ci = 0.22 - 0.67 ) , the present study shows 90.7% mortality in severe disease patients which when compared is higher than that reported in turkey ( 50.8% ) . this is possibly because of delayed referral and initiation of antiviral drug . highest positive cases ( 124 ) were reported during january , followed by decline upto march 2010 . it signifies the relationship between influenza virus and cold season , as maximum number of cases occurs during these months of winter season . the second wave had started in monsoon season , suggesting that high humidity may favor the spread of influenza a ( h1n1 ) . present study reported that majority of the patients in both categories had cough , fever , shortness of breathing , and sore throat , likewise patients of us and canada . current study reported that 42.5% severe influenza a ( h1n1 ) patients have any one coexisting condition ( or = 0.53 . ci = 0.31 - 0.90 ) , which was 53% in france , and 57.7% in china . pregnancy was a well documented risk factor for severe infection and death in seasonal influenza and in previous pandemics . in this study , pregnancy was reported as a risk factor ( or = 0.22 , ci = 0.06 - 0.76 ) in 11.5% severe influenza a ( h1n1 ) cases than among non - severe influenza a ( h1n1 ) cases . out of ten severe disease pregnant cases , two were in second trimester and eight were in third trimester . pneumonia was reported more among patients with severe disease ( 86.7% ; or = 0.30 , ci = 0.16 - 0.53 ) , higher than that reported in korea ( 70.7% ) and brazil . in absence of accurate diagnostic methods , patients who were hospitalized with suspected influenza and lung infiltrates on chest radiography therefore , patients who were infected in the community and did not go to the hospital were not included in our study . all diagnostic testing was clinically driven , and other investigations were not obtained in a standardized fashion . despite the use of a standardized data collection form , not all information was collected for all patients . considering association between coexisting condition and severity of disease , it is possible that the presence of a coexisting condition that makes icu admission more likely might also have made ascertainment of virologic infection , thus producing an inflated estimate of any potential association . with regards to the present study , the relative impact of the direction of this type of selection bias , known as berksonian bias , is uncertain . therefore , patients who were infected in the community and did not go to the hospital were not included in our study . all diagnostic testing was clinically driven , and other investigations were not obtained in a standardized fashion . despite the use of a standardized data collection form , not all information was collected for all patients . considering association between coexisting condition and severity of disease , it is possible that the presence of a coexisting condition that makes icu admission more likely might also have made ascertainment of virologic infection , thus producing an inflated estimate of any potential association . with regards to the present study , the relative impact of the direction of this type of selection bias , known as berksonian bias , is uncertain . the severity of illness among influenza a ( h1n1 ) infected patients was associated with delayed referral from general practitioner / physician , duration of antiviral treatment , and presence of coexisting condition , especially pregnancy . these findings may be different during the future waves , owing to the timely deployment of an effective vaccine , to viral mutation , and resistance to antiviral drugs .
background : in india , the first case of 2009 pandemic influenza a ( h1n1 ) virus infection was reported in may 2009 and the same in saurashtra region in august 2009 . 
 we describe the epidemiology and factors associated with severe and non - severe cases of 2009 influenza a ( h1n1 ) infection reported in the saurashtra region.materials and methods : from september 2009 to january 2011 , we reported 511 patients who were infected with 2009 influenza a ( h1n1 ) virus and admitted in different hospitals of rajkot city . 
 real - time reverse transcriptase polymerase chain reaction ( rt - pcr ) testing was used to confirm infection . 
 factors associated with severe cases were determined by comparing with non - severe cases.results:out of 511 patients , 140 had severe disease ( requiring intensive care or died ) and 371 non - severe diseases ( admitted in wards and survived ) . 
 median age of 30 years ; median time of 5 days from onset of illness to diagnosis , and 4 days median time was reported for hospital stay among severe disease patients . 
 more than half ( 60.7% ) were females . 
 out of the patients with severe disease , 52.1% patients residing in urban area ( or = 1.68 , ci = 1.13 - 2.49 ) . 
 significant association was reported among severe disease patients for delayed referral from general practitioner / physician after initial treatment . 
 all patients received antiviral drug , however , only 27.1% received within 2 days of illness . 
 presence of coexisting condition ( pregnancy ( or = 0.19 , ci = 0.08 - 0.48 ) was strongly associated with severe disease.conclusion:delayed referral from general practitioner / physician , duration of antiviral treatment , presence of coexisting condition ( i.e. , pregnancy ) were responsible for intensive care or mortality among severe influenza a ( h1n1 ) illness .