2 Cheraghi

JRHS 2010; 10(1): 15-21

Copyright © Journal of Research in Health Sciences        

Influenza A (H1N1) in Hamedan Province, Western Iran in 2009: A Case-Control Study

Zahra Cheraghia, Amin Doosti Irania, Shahab Rezaieana, Jamal Ahmadzadeha, Jalal Poorolajalb*, Hossein Erfanic, Jalal Battaeic, Ali Zahiric, Norooz Ali Noroozic, Ali Golshaeianc, Mostafa Anvaric, Ali Neshanic, Hamid Padyarc, Ali Mohammad Reza Alipoorc, Mohsen Moradic, Mahdi Malekic, Samad Givic, Morad Esmaeilic.

a Department of Epidemiology & Biostatistics, School of Public Heath, Hamedan University of Medical Sciences, Hamedan, Iran

b Department of Epidemiology & Biostatistics, School of Public Heath and Research Center for Health Sciences, Hamedan University of Medical Sciences, Hamedan, Iran

c Deputy of Health, Hamedan University of Medical Sciences, Hamedan, Iran

* Corresponding author: Poorolajal J (MD, PhD), E-mail addresses: poorolajal@umsha.ac.ir

Received: 11 April 2010, Revised: 26 April 2010, Accepted: 15 May 2010, Available online: 21 June 2010        


Background: The novel influenza A (H1N1) virus was first detected in March 2009 in Mexico and then disseminated to many other countries worldwide. In this study, we assessed the potential risk factors of swine flu as well as the most important clinical manifestations of this infectious disease among confirmed cases during early phase of pandemic H1N1.

Methods: Subjects (cases and controls) were selected from those patients with signs and symptoms of respiratory tract infection who referred to health centers of eight cities throughout Hamedan Province, western Iran form July to December 2009. Characteristics of the participants were obtained by interviewers using pre-determined questionnaire. Cases were distinguished by pharyngeal soap speci­mens positive for influenza A virus using polymerase chain reaction (PCR). Logistic regression model was conducted at 0.05 significance level using Stata 9.1 statistical software to assess the effects of various risk factors on H1N1 influenza infection.

Results: Totally, 245 confirmed cases of H1N1 influenza were compared with 388 controls. Case fatality rate of influenza infection was about 2.86%. In comparison with age group of 1-19 yr old, adjusted odds ratio estimates was 1.91 [95% CI: 1.06, 3.46] for age group of 20-39 yr old, 0.94 [0.37, 2.38] for age group of 40-59 yr old, and 0.34 [0.09, 1.37] for age group of 60-79 yr old. Adjusted odds ratio estimates of influenza A infection was 8.12 [95% CI: 3.11, 21.6] for pregnant women compared to non-pregnant women; 1.84 [95% CI: 1.32, 2.86] for high educated individuals in comparison with low educated individuals; 2.11 [95% CI: 1.25, 3.57] for whose who had close contact with suspected influenza patients; and 2.15 [95% CI: 1.16, 3.98] for individuals with normal body mass index (BMI= 25-30) compared with underweight individuals (BMI< 20). There were no significant differences in clinical manifestations between cases and controls.

Conclusion: The risk of influenza A infection is highest among children and adolescents, pregnant women, high educated individuals, and those who had close contact with suspected influenza patients during pandemic phase. In addition, there is no pathogonomonic sign or symptom to distinguish influenza infection clinically from other kinds of respiratory track infections.

Keywords: Influenza A (H1N1), Case-Control Studies, Clinical manifestations, Iran                


The swine influenza is an acute and highly contagious respiratory tract infec­tion that is produced by influenza A (H1N1) virus [1]. The new influenza A (H1N1) vi­rus spreads from person-to-person. It is trans­mitted like sea­sonal flu during close contact with infected in­di­viduals. The infected droplets expelled during cough­ing or sneezing [1]. The in­cubation as well as in­fectious periods are usu­ally short from 1 to 3 days and from 3 to 5 days respec­tively, although in­fec­tious period in children may persist until 7 days [2].

Influenza A (H1N1) has multiple clinical signs and symptoms including fever, cough, myal­gia, and sore throat [3, 4]. The children less than 5 or greater than 65 yr old, pregnant women, indi­vi­duals who suffer from chronic dis­ease, and the im­mune compromised people are at higher risk of infection in comparison with general po­pula­tion [5]. In addition, influ­enza A increases ma­ternal and neonatal morbid­ity and mortality rate [6].

The novel H1N1 virus was first detected in March 2009 in Mexico and then disseminated to the US and many other countries worldwide. On 11 June 2009, the World Health Organiza­tion (WHO) declared pandemic influenza phase 6 [7]. Soon after that, in 10 July 2009, H1N1 influ­enza infection spread worldwide and at least 100,000 persons were infected by this novel H1N1 influ­enza virus [8]. Investigators pre­dicted if this pan­demic achieves virulence strong enough like 1981 pan­demic flu, 62 mil­lion death would occurred [9].

The first case of H1N1 swine flu in Iran was detected in a student who lived in the US  and came back to Iran for summer vacation and de­vel­oped symptoms less than a week after his ar­rival [10]. From June to November 2009, 2662 confirmed influenza infected individuals were re­ported in Iran [11].

In his case-control study, we intended to assess the potential risk factors of H1N1 influ­enza A as well as the most important clinical signs and symptoms of this disease among con­firmed cases detected in Hamedan province dur­ing early phase of pandemic H1N1.


This unmatched case control study was con-ducted in Hamedan Province, western Iran in­cluding 245 cases and 388 controls. Both cases and controls were selected from those pa­tients with signs and symptoms of respiratory tract infection who referred to health centers of eight cities throughout Hamedan province dur­ing the early pandemic phase of swine flu form July to December 2009. Pharyngeal soap and gar­gle specimens were taken form all subjects un­der study for detection of influenza A (H1N1) virus. The specimens were sent to cen­tral laboratory of Ministry of Health in Tehran. All specimens were tested for H1N1 influenza A using poly­merase chain reaction (PCR). Those individuals whose specimens were posi­tive for H1N1 influ­enza were considered as cases otherwise as con­trols. Simultaneously, char­acteristics of the par­ti­cipants as well as data regarding to potential risk factors were col­lected by interviewers using a pre-determined questionnaire.

The potential risk factors of H1N1 influenza infection that were evaluated in this study in­cluded: age, body mass index (BMI), smoking, close contact with suspected influenza patients, chronic disease including coronary heart dis­ease (CHD), chronic obstructive pulmonary dis­ease (COPD), dia­betes, dialysis, cancer, ane­mia, and transplan­ta­tion, and history of influ­enza vaccination. Cli­nical signs and symptoms documented at the time of taking specimen and in­cluded fever, cough, sore throat, headache, rhi­norrhea, fatigue, nausea, diar­rhea, and abdomi­nal pain. In addition, sever­ity and sud­denly onset of signs and symptoms were as­sessed.

Data were collected during five months follow- up. We conducted logistic regression model at 0.05 significance level using Stata 9.1 statistical soft­ware to assess the effects of vari­ous risk factors on H1N1 influenza infection. We considered ad­justed odds ratios (OR) to as­sess covariates ef­fects on influenza infection.


In this study, 245 confirmed cases of H1N1 influenza patients were compared with 388 non-influenza patients with clinical signs and symp­toms of respiratory tract infection (Table 1). Seven deaths occurred among 245 cases (Ta­ble 2). Accordingly, case fatality rate of influ­enza A infection was estimated to be 2.86%.

Table 1: Distribution of demographic characteristics and potential risk factors among cases and controls



Cases (%)

Controls (%)

Age (yr)


57 (23)

70 (18)


59 (24)

123 (32)


73 (30)

77 (20)


24 (10)

40 (10)


19 (8)

23 (6)


5 (2)

16 (4)


4 (2)

13 (3)


3 (1)

17 (4)


1 (0)

8 (2)



107 (44)

184 (47)


138 (56)

204 (53)



30 (22)

20 (10)


108 (78)

184 (90)









6 (2)

6 (2)



8 (3)

43 (11)

Primary school

42 (17)

98 (25)

Middle school

30 (12)

85 (22)

High school

52 (21)

93 (24)


31 (13)

33 (8)


41 (17)

33 (8)


41 (17)

3 (1)



26 (15)

28 (5)


51 (29)

136 (39)


10 (6)

9 (3)


1 (1)

2 (1)


49 (28)

94 (27)


3 (2)

4 (1)


13 (7)

21 (6)


20 (11)

55 (16)


2 (1)

1 (1)


0 (0)

3 (1)

Chronic disease


20 (8)

45 (12)


225 (92)

243 (88)



6 (2)

32 (8)


191 (78)

356 (92)


48 (20)

0 (0)



84 (34)

259 (67)


41 (17)

92 (24)


12 (5)

14 (3)


108 (44)

23 (6)

End outcome


238 (97)

388 (100)


7 (3)

0 (0)

Table 2: Characteristics of the cases who died from influenza A (H1N1) infection



Number (%)

Age (yr)


1 (14)


1 (14)


1 (14)


2 (28)


2 (28)



4 (57)


3 (43)



0 (0)


7 (100)



2 (29)


5 (71)



1 (14)


5 (71)


1 (14)



1 (14)


6 (86)



2 (29)


2 (29)


3 (42)

The effect of various potential risk factors on influenza infection was investigated using ad­justed odds ratio (OR) (Table 3). Based on these findings, Compared to children and adoles­cents aged 1-19 yr, adjusted odds ra­tio estimate was 1.91 [95% CI: 1.06, 3.46] for adults aged 20-39 yr, 0.94 [95% CI: 0.37, 2.38] for adults aged 40-59 yr, and 0.34 [95% CI: 0.09, 1.37] for eld­ers aged 60-79 yr. Although an apparent in­creased risk of influenza infection was seen among fe­males [OR= 1.20; 95% CI: 0.70, 2.01], however, the as­socia­tion was not statistically sig­nificant (P= 0.514). On the other hand, the crude OR of influenza A in­fection for pregnant women compared with non-pregnant women was 2.91 [95% CI: 1.57, 5.42], the adjusted OR estimate increased tremen­dously and reached 8.12 [95% CI: 3.11, 21.6].

Table 3:  The effect of various potential risk factors on influenza A (H1N1) infection


Adjusted OR [95% CI]


Age (20-39 years/1-19 years)

1.91 [1.06, 3.46]


Age (40-59 years/1-19 years)

0.94 [0.37, 2.38]


Age (60-79 years/1-19 years)

0.34 [0.09, 1.37]


Sex (female/male)

1.02 [0.61, 1.72]



8.12 [3.11, 21.6]


Educationa (high educated/low educated)

1.84 [1.32, 2.86]


Suspected contact (yes/no)

2.11 [1.25, 3.57]


Smoking (smokers/nonsmokers)

0.39 [0.13, 1.18]


Region (urban/rural)

1.22 [0.71, 2.10]


Chronic disease (yes/no)

2.10 [0.95, 4.67]


Trip (yes/no)

1.01 [0.57, 1.79]


Influenza vaccination (yes/no)

0.81 [0.23, 2.83]


BMI (normal weight/low weight)

2.15 [1.16, 3.98]


BMI (overweight/low weight)

1.40 [0.65, 3.05]


a low education level included: illiterate, primary school, and middle school; high education level included high school and academic.

We divided the participants into six groups according to their education level including il­lit­er­ate, primary school, middle school, high school, and academic. There were no statisti­cally sig­n­ificant differences between the chance of in­flu­enza infection either among the first three sub­groups (illiterate, primary school, and middle school) or between the last two sub­groups (high school and academic). Therefore, we combined the first and second homogenous subgroups and made two distinct subgroups in­cluding low edu­cated individuals versus high-educated indivi­duals respectively. Unexpect­edly, adjusted OR estimate for high educated indi­viduals was 1.84 [95% CI: 1.32, 2.86] com­pared to low educated individuals.

The adjusted OR estimate of influenza A in­fection was 2.11 [95% CI: 1.25, 3.57] for those individuals who mentioned a history of close contact with suspected influenza patients during the last week. In addition, unlike to our ex­pectation, the risk of influenza infection was higher among non-smokers compared to smok­ers, although the association was not statisti­cally significant (P= 0.095).

Based on these findings, the adjusted OR estimate was 1.22 [95% CI: 0.71, 2.10] for ur­ban population compared to rural population (P= 0.461); 2.10 [95% CI:  0.95, 4.67] for peo­ple with positive history of chronic disease com­pared with general population (P= 0.068); and 1.01 [95% CI: 0.57, 1.79] for those who had a trip during the last week compared with those who did not have a trip (P= 0.972). In addi­tion, there was not statistically difference be­tween risk of influenza infection among recipi­ents of sea­sonal influenza vaccine in com­pari­son with those who had not received the vaccine (P= 0.739).

Compared with underweight individuals with body mass index (BMI) <20, adjusted OR esti­mate for individuals with normal body mass in­dex (BMI= 20-25) was 2.15 [95% CI: 1.16, 3.98] and for overweight individuals (BMI> 25) was 1.40 [95% CI: 0.65, 3.05].

Clinical signs and symptoms, which were eva­luated among cases and controls, included fe­ver, sore throat, cough, headache, rhinorrhea, fa­tigue, nausea, diarrhea, and abdominal pain (Ta­ble 4  and Figure 1). There were no statisti­cally signifi­cant dif­fer­ences in the proportion of clinical signs and sy­mp­toms between cases and controls. Al­though cli­nical signs and symptoms initiated more sud­denly among cases (56%) than among con­trols (47%), but the dif­ference was not statisti­cally significant (P= 0.061).

About 30% of the cases and 25% of the con­trols were hospitalized. In addition, 9% of the cases and 4% of the controls were hospital­ized in in­tensive care unit (ICU).

Table 4: Distribution of influenza A (H1N1) signs and symptoms among cases and controls

Clinical sign/Symptom

Proportion among



Cases [95% CI]

Controls [95% CI]

Sudden onset

0.56 [0.47, 0.64]

0.47 [0.42, 0.52]



0.80 [0.73, 0.86]

0.81 [0.77, 0.85]


Sore throat

0.52 [0.44, 0.59]

0.59 [0.54, 0.64]



0.68 [0.61, 0.75]

0.63 [0.59, 0.68]



0.35 [0.28, 0.43]

0.41 [0.36, 0.45]



0.24 [0.17, 0.31]

0.25 [0.21, 0.30]



0.62 [0.57, 0.68]

0.62 [0.57, 0.67]



0.21 [0.15, 0.27]

0.20 [0.16, 0.24]



0.15 [0.09, 0.20]

0.12 [0.09, 0.15]


Abdominal pain

0.22 [0.16, 0.29]

0.16 [0.12, 0.20]


Figure 1: Distribution of clinical signs and symptoms in among cases  and controls


According to the results of present study, pregnant women, urban population, high edu­cated people, obese individuals, and those who mentioned close contact with suspected influ­enza patients were at higher risk of H1N1 influ­enza A infection. 

Selection of controls from the patients with res­piratory tract infection made them clinically similar to cases. However, because of logistic and financial limitation, it was not possible to se­lect another control group from those non-patients clienteles who referred to health cen­ters for other reasons.

In this study, pregnancy was detected as the strongest risk factor for influenza A infection. Ac­cordingly, although pregnant women my be at higher risk if influenza infection [6], one rea­son that may explain such strong association is intensive health care that was conducted during early phase of pandemic H1N1 to detect preg­nant women infected with influenza A. This prac­tice introduced many pregnant women in the study participants so that pregnant women comprised 15.6% of the female participants. A relatively si­milar result was indicated in WHO re­port. This report stated that pregnant women had 13 times higher risk for hospitalizing due to influ­enza A in comparison with non-pregnant women [6].

Adults aged 40-59 yr and 60-79 yr had lower risk of influenza A infection in com­parison with children and adolescents aged 1-19 yr. In other words, risk of influenza infec­tion decreases with age. Nonetheless, adults aged 20-39 yr had higher risk of infection compared to children and ado­lescents. It may be attributed to greater propor­tion of high-risk pregnant women aged 20-39 yr among this age group.

We found an apparent inverse association be­tween cigarette smoking and influenza infec­tion so that the chance of influenza infection among non­smokers was nearly two times higher than among smokers. Although the asso­ciation was not sta­tis­tically significant, this may be the result of chance error due to sparse data in our study. As it was in­dicated in Table 1, only six out of 245 cases were smokers. Such small num­ber of data can lead to chance error.

As mentioned in the results section, adjusted OR estimates was statistically significant for high-educated individuals compared with low edu­cated individuals. This increased risk of infec­tion among high-educated individuals can be attributed to their occupation, which was not evaluated in this study. The occupation of the par­ticipants was not evalu­ated in this study be­cause of sparse data due to di­versity of the occu­pations among the partici­pants. 

We indicated that incidence of influenza in­fection was higher among individuals with po­si­tive history of chronic disease. However the as­sociation was not statistically significant (P= 0.127). This may also be due to sparse data, because only 20 out of 245 cases suffered from chronic diseases (Table 1).

A study conducted in California indicated that 35% of the cases had COPD, 17% were dia­betic, and 17% had CHD [12]. Based on our findings, 11% of the cases suffered from at least one type of chronic diseases. Prevalence of chro­nic diseases among the cases reported by Cali­fornia study was much higher than our study. A reason that may explain this discrep­ancy is that the population of US is older than Ira­nian po­pulation. Thus, prevalence of chronic diseases is expected to be higher among US population.

A matched case-control study conducted in Mexico city revealed that none of the individu­als in control group who had received seasonal in­fluenza vaccine had not been infected with in­fluenza A [13]. In our study, six individuals among cases group had already received sea­sonal in­fluenza vaccine. This discrepancy may be due to sparse data in our study (only 6 out of 245 cases in our study received influenza vac­cine).

Previous studies indicated that traveling had important role in increasing the incidence of influ­enza A infection [13]. In addition, the first re­port of confirmed cases of H1N1 2009 influ­enza in Iran confirmed this subject and revealed that 70% of the cases had either a history of trav­eling aboard during the last two weeks or having direct contact with someone who re­turned from abroad [11]. In this study, we indi­cated that there was not statistically significant positive relation between traveling abroad and in­fluenza infection (P= 0.996). In addition, our findings revealed that the close contact to sus­pected influenza patients may increase nearly two times the chance of influenza infection.

One study that conducted in England estimated the overall case fatality rate of influ­enza infec­tion to be 26 per 100,000.  This esti­mate for children 5-14 yr old was reported to be the lowest (11 per 100000) and for elder over 65 yr old was esti­mated to be the highest (980 per 100000). The age mean of those who died due to influenza in­fection was 39 yr [14]. An­other study that con­ducted in New York indi­cated that 62% of deaths were between 25-49 yr old with age mean 41.5 yr [15]. According to our findings, the age median of the cases was 35.57 yr which was rather younger than what re­ported in previous studies [14].

The similarity of clinical characteristics of cases and controls were because of selecting the con­trol group from patients with respiratory tract in­fection who were clinically similar to cases at the enrolment in the study. We indi­cated that there is not a prominent clinical sign or symptom to dis­tinct the cases from the con­trols. Two studies in Mexico and the US re­ported similar results and stated that there is no pathognomonic sign or sy­mptom to distinguish in­fluenza infection clini­cally from other respira­tory tract infections [16].


According to the results of this study, we con­cluded that, children and adolescents, preg­nant women, high-educated individuals, and those who had close contact with suspected influ­enza pa­tients during the acute pandemic phase may be considered to be at higher risk of in­fluenza A in­fection. In addition, there is no pathogonomonic sign or symptom to distin­guish influenza infec­tion clinically from other kinds of respiratory track in­fections. We also indi­cated that case fatality rate of influenza infec­tion is estimated to be 2.86%. In addition, there is no pathogonomonic sign or symptom to distinguish influenza infection clini­cally from other kinds of respiratory track infections.


We would like to thank all health experts and health technicians of the Deputy of Health, Ha­medan University of Medical Sciences who col­laborated in data collection during the early phase of pandemic H1N1 influenza infection as well as De­puty of Research and Technology for financial sup­port of this study. The authors de­clare that they have no conflicts of interest.


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