Abstract

Background: In 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009–2010.

Methods: A multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10 months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections.

Results: A total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20 years was significantly higher than that among patients in other age groups (p < 0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7 days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group.

Conclusion: Our prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed.

Introduction

In 2009, infections with influenza A (H1N1) virus spread worldwide.1 Although the most common symptoms are cough and fever, which are uncomplicated influenza-like symptoms, the World Health Organization (WHO) reported that more than 10,000 individuals worldwide died from the infection. Recent studies indicated that fatality ratio in influenza A (H1N1) virus infection seems to be higher than that of seasonal influenza infections.2,3 The WHO identified age < 65 years, immunosuppression, and chronic medical condition as being the specific risks for influenza A (H1N1) infections. These factors are relevant to ulcerative colitis and Crohn's disease4 because majority of patients with IBD are younger and they have often been treated with steroids, thiopurine, tacrolimus, methotrexate, and biological treatments.

In general, the risk factors for the complications of infectious diseases in inflammatory bowel disease (IBD) patients are either therapy-related or non-therapy-related.5,6 Non-therapy-related factors include malnutrition and advanced age, whereas therapy-related factors include operations, immunosuppressive treatment, and leukocytopenia caused by immunomodulators. Patients with IBD are at a higher risk for opportunistic infections711 because of the suppression of their immune systems. A previous study has indicated that the combined use of the immunosuppressants is associated with an increased risk of opportunistic infections.7 Patients who are on immunomodulators and biologics should be considered to be at high risk for complications from influenza A (H1N1) infections.2 However, no data exist on the incidence of H1N1 influenza infections in patients with IBD.12 It is unclear whether IBD patients who are treated with immunomodulators/biologics are more susceptible to infection with H1N1 influenza virus than IBD patients who are not treated with these drugs.

The aim of this study was to prospectively assess the incidence of H1N1 influenza infections from 2009 to 2010. We also assessed the age distribution and risk factors associated with H1N1 virus infections in IBD patients.

Patients and methods

Study design and patient populations

This was a prospective study involving IBD patients at 4 institutions in Japan (Tokyo Medical and Dental University Hospital, Yokohama City University General Hospital, Social Insurance Center General Hospital, and Showa University Hospital). No in-patients were included in this study. A total of 570 patients were enrolled in this study from September to December 2009 (Table 1). The numbers of ulcerative colitis (UC) and Crohn's disease (CD) patients were 371 and 187, respectively. Indeterminate colitis patients (n = 11) were also enrolled. Patients were followed up for new influenza infections during the study period, which ended during September 2010. The protocols in this study were approved by the ethical review boards of all of the institutions, and patients aged < 20 years old were allowed to be enrolled in the study if the patients and their parents agreed.

Case–control study

To assess the effect of medication on the rate of H1N1 influenza infections, a nested, case–control study was performed. For the case group, patients with H1N1 influenza infections were selected. At every clinic visit, the patients were asked whether they had developed H1N1 influenza infections. All influenza-infected patients were diagnosed based on both clinical symptoms (such as fever, fatigue, sore throat, runny nose, muscleache, and headache) and laboratory tests. Rapid diagnostic tests can detect influenza A and influenza B viruses and distinguish between them. Specimens were obtained using nasopharyngeal swabs. Influenza infections were mostly diagnosed at each institution and these were also diagnosed at other hospital/clinics except 4 institutions (e.g. general practitioner).

Two uninfected patients were selected as controls and were matched based on age (with an interval of 10 years; ≦ 19, 20–29, 30–39, 40–49, and ≧ 50 years-old). Controls were required to visit their clinics within 2 weeks before or after the infections were observed in the matched patients.

Data acquisition

The patients' demographic data included their current age, age at diagnosis, current smoking habits, type of disease (UC or CD) and medical treatments during the follow-up period. All patients were classified as UC or CD according to previously established criteria.13 In the present study, patients were asked whether H1N1 influenza vaccinations were administered at each clinic. We also asked whether patients with H1N1 influenza infections had used antiviral treatments. The duration of H1N1 influenza symptoms (which were less than 7 days, 7–14 days, or more than 14 days) and hospital admissions due to H1N1 influenza infections was also assessed.

The use of infliximab was recorded when patients were treated with it within 8 weeks of the infectious episode or the index date. Because health insurance did not cover the expenses associated with adalimumab and certolizumab, these treatments were not studied (although adalimumab could be used after October 2010). The use of 5-aminosalicylates, corticosteroids, and tacrolimus was recorded when patients were administered these agents within 2 weeks of the infectious episode or the index date. The use of other medications (including azathioprine, 6-mercaptopurine (6-MP) and methotrexate) was recorded when these agents had been used within 12 weeks of the H1N1 influenza episode or the index date. For infected and control cases, each medical treatment was recorded. For example, if a H1N1 influenza infection was observed in December 2009 and the patient had used 5-ASA and corticosteroids within 2 weeks prior to the infection, it was recorded that 5-ASA and corticosteroids were used for that patient. The use of medications in matched controls was also recorded during the same period.

Data analysis and statistical methods

The incidence and age distribution of patients with H1N1 influenza infections were assessed. The age distribution of H1N1 influenza infections in the general population was obtained from a report of the Japanese Infectious Disease Surveillance Center. In the case–control study, the gender, duration of disease, type of disease, and medication use (including mesalamine, corticosteroids, thiopurine, infliximab, methotrexate and tacrolimus) during the infection or on the index date were compared between patients with infections (case) and those without infections (control) to assess the effects of medication use on the incidence of infections. The percentage of patients who used any immunomodulators (any IM) or 2 types of IM was also compared between the case and control groups. Any IM was defined as the use of at least one of the following medications: steroids, infliximab, thiopurine, tacrolimus or methotrexate. A total of 36 cases and 2 controls per case were required to detect an odds ratio of 2.0 if 30% of patients in the control group were estimated to use immunomodulators.

For statistical analyses, the differences in ages between two groups were tested using a t-test, and the differences in the incidence of other factors (e.g., sex, and type of disease) between two groups were tested using chi-squared tests and Fisher's exact test. The significance level in all tests was < 5%. All data were analyzed using SPSS version 18 (SPSS Corp., Tokyo, Japan).

Results

Younger age was associated with an increased risk of H1N1 influenza infections in IBD patients

The patients' clinical features are provided in Table 1. A total of 38 patients ((6.7%) 95% Confidence Interval [CI] (4.6–8.8%)) were infected with H1N1 influenza virus. Type B influenza virus infections were found in 2 patients, respectively. Antiviral treatments were used in 20 patients (53%), whereas other patients' symptoms improved without antiviral treatments. In all cases, hospital admission was not required because of influenza infections. Twenty-nine patients (76%) recovered from the influenza symptoms within 7 days. Seven patients continued to have symptoms for more than 7 days. As expected, most of these infections occurred in young patients (Fig. 1). Almost quarter of the IBD patients (12 of 45 patients, 26.7%) who were less than 20 years old were infected with the H1N1 influenza virus. The incidence of H1N1 influenza infections in patients who were less than 20 years old was significantly higher than that of other patients (Fig. 1) (P < 0.01, OR: 6.9, 95% CI: 3.2–14.9).

Risk factors for H1N1 influenza infections in IBD patients

For H1N1 influenza infections, the patient's clinical features and the use of medications are provided in Table 2. Because H1N1 influenza virus infection was mainly investigated in this study, 2 patients who were infected with Type B influenza virus were excluded. Although the patients in the control group were not matched to cases based on gender, duration of disease, type of disease (UC or CD), or the use of medications for IBD, these factors were comparable in both groups (Table 2). In our study, only 13% of the cases (5 of 38 patients) received H1N1 vaccines before they developed influenza infections. These 5 patients received a dose of H1N1 vaccination and all vaccinations were given within 2 weeks prior to H1N1 influenza infections. In the control group, 12 of 76 patients (15.7%) received H1N1 vaccines before the index dates. This indicated that most of the H1N1 influenza infections were spread before the H1N1 vaccine was available from 2009 to 2010.

To assess the effect of immunomodulators on H1N1 influenza infections, we considered the use of thiopurine, infliximab, tacrolimus, and methotrexate to be the use of any immunomodulators (any IM). The percentage of patients who used steroids or thiopurine was comparable between the cases and the control group (Table 2). We also confirmed that the percentage of patients who used any 2 IM (e.g., infliximab and 6-MP) was also comparable between both groups. In the present study, no patients needed hospitalization due to H1N1 influenza infection, although the steroids, thiopurine, and infliximab were used. The percentage of the need for antiviral treatments and duration of H1N1 influenza symptoms in patients with or without any IM has been compared (Table 3).

Discussion

In the spring of 2009, 2 cases of human infections with influenza A (H1N1) were reported, and the WHO declared a pandemic phase level 6.1 In Japan, the first patients were reported at the end of April. The Japanese Ministry of Health, Labour and Welfare reported that approximately 140,000 persons were infected and 127 patients died. This terrible pandemic also caused IBD patients to become anxious, especially the IBD patients who were on immunomodulators and biologics. In this study, the incidence of H1N1 influenza infections in IBD patients was investigated. Most of the H1N1 influenza infections were observed in younger patients. Our study indicated that the incidence of H1N1 influenza infections during the 2009–2010 season was 6.7% in IBD patients. National Infectious Disease Surveillance Center reported that estimation of H1N1 incidence was 8.4% (approximately 10.7 million patients) in general population. The incidence of H1N1 influenza infections in our patients (6.7%, 95% CI 4.6–8.8%) was comparable to that in Japanese general population.

For decades, influenza infections occurred predominantly in older and immunocompromised patients. However, our study indicated that the incidence of H1N1 influenza infections was significantly higher in patients who were < 20 years than that among other patients. Several studies reported that most patients for H1N1 influenza infection were aged from 5 to 18 years in general population.1416 The vast majority of H1N1 influenza cases in all country had occurred among adolescents and young adults. The median age of pandemic (H1N1) 2009 influenza-infected patients was lower than that of seasonal influenza A (H3N2)-infected patients.14 Another study also reported that the percentage of positivity of pandemic (H1N1) 2009 influenza virus was highest in 5–18 year age groups (OR 2.5 for > 35 years age group) when compared to seasonal influenza.13 Data compiled by WHO indicated that approximately 25% of cases were aged 0–9 years, 36% were aged 10–19 years, 17% were aged 20–29 years, 9% were aged 30–39 years, 7% were aged 40–49%, and 5% were aged > 50 years.17 These results consisted with our result indicating that age distribution of H1N1 influenza infections between IBD patients and the general population was comparable (Fig. 2).

We failed to find that the incidence of H1N1 influenza infections in the 2009–2010 season was higher in patients who were on any immunomodulators than in patients who were not on any immunomodulators. These results may indicate that having a less healthy immune system does not imply an increased risk for H1N1 influenza infection during pandemic exposure while patients who were on immunomodulators might increase the risk of complications of H1N1 influenza infection.

In this study, 5 of 38 patients received the H1N1 vaccines before the influenza infections. One possibility of non-response to the vaccine in these patients was due to short duration between vaccination and H1N1 influenza infections.

There were limitations to this study. First, we could not distinguish H1N1 infections from seasonal influenza infections. From August 2009 to March 2010, the Infectious Disease Surveillance Center reported that influenza AH1 (Russian type), AH3 (Hong Kong Type), B and H1N1 infections had occurred in 18 (0.06%), 153 (0.52%), 35 (0.12%) and 28,939 (99.29%) patients, respectively. Thus, most of the influenza type A viruses in our study may have been H1N1 viruses. Second, we only included cases of H1N1 influenza infections that occurred after enrollment in this study to obtain more exact information from our prospective observations. It is assumed that some H1N1 influenza infections that occurred prior to enrollment were missed. Finally, some patients with H1N1 influenza infections who only showed symptoms may also have been missed. However, only influenza-like symptoms misled our diagnoses because it is difficult to distinguish between influenza and influenza-like bronchitis or pharyngitis.

Our study indicated that the incidence of H1N1 influenza infections in 2009–2010 was 7 times higher in IBD patients aged < 20 years than other IBD patients. Younger IBD patients would increase the probability of transmission due to the close proximity at school and university, compared to other populations.14 Furthermore, older patients may have cross-immunoreactivity for H1N1 pandemic influenza virus.14,18,19 Previous study indicated that pandemic 2009–2010 H1N1 influenza infections were associated with a higher percentage of severe cases and mortality.20 Other report also showed that 28% of H1N1 influenza infected-IBD patients needed to be hospitalized and 3 (12%) of 25 patients were sent to intensive care unit.21 On the other hand, our study showed that it was relatively mild among IBD patients and no hospitalization was required. The probable explanation for this result is frequent visits to the hospital among IBD patients. As a result, early diagnosis could be done in most cases and antiviral treatment might be given at the appropriate time.

Conflict of interest statement

Potential competing interest: None.

Financial support: This work was supported in part by Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare of Japan.

Acknowledgments

The authors would like to express their thanks to Nature Publishing Editing for editing the manuscript for English language readability.

Specific author contributors

Makoto Naganuama (MN) and TF have equally contributed to this study and were involved in conceptualizing the study. MN and TF designed the main part of this study and drafted the manuscript. MN, TF, RK, NY, YT, and Masakazu Nagahori were involved in the acquisition of data. K.A. and T.T. advised us on the statistical analyses. MW organized the study and provided specific comments. All authors read and approved the final manuscript.

References

1
Ginsberg
M.
Hopkins
J.
Maroufi
A.
Dunne
G.
Sunega
D.R.
Giessick
J.
et al
Swine influenza A (H1N1) infection in two children — Southern California, March–April 2009
MMWR Recomm Rep
 
58
2009
400
402
2
Rahier
J.F.
Yazdanpanah
Y.
Viget
N.
Travis
S.
Colombel
J.F.
Review article: influenza A (H1N1) virus in patients with inflammatory bowel disease
Aliment Pharmacol Ther
 
31
2010
5
10
3
Fraser
C.
Donnelly
C.A.
Cauchemez
S.
Hanage
W.P.
Van Kerkhove
M.D.
Hollingsworth
T.D.
et al
Pandemic potential of a strain of influenza A (H1N1): early findings
Science
 
324
2009
1557
1561
4
Cullen
G.
Bader
C.
Korzenik
J.R.
Sands
B.E.
Serological response to the 2009 H1N1 influenza vaccination in patients with inflammatory bowel disease
Gut
 
61
2012
385
391
5
Epple
H.J.
Therapy- and non-therapy-dependent infectious complications in inflammatory bowel disease
Dig Dis
 
27
2009
555
559
6
Aberra
F.N.
Lichtenstein
G.R.
Methods to avoid infections in patients with inflammatory bowel disease
Inflamm Bowel Dis
 
11
2005
685
695
7
Toruner
M.
Loftus
E.V.
Jr.
Harmsen
W.S.
Zinsmeister
A.R.
Orenstein
R.
Sandborn
W.J.
et al
Risk factors for opportunistic infections in patients with inflammatory bowel disease
Gastroenterology
 
134
2008
929
936
8
Viget
N.
Vernier-Massouille
G.
Salmon-Ceron
D.
Yazdanpanah
Y.
Colombel
J.F.
Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis
Gut
 
5
2008
549
558
9
Afif
W.
Loftus
E.V.
Safety profile of IBD therapeutics: infectious risks
Med Clin North Am
 
94
2010
115
133
10
Tone
M.
Renna
S.
IBD: incidence of HSV and HPV with azathioprine
Nat Rev Gastroenterol Hepatol
 
6
2009
444
445
11
Lawrance
I.C.
Radford-Smith
G.L.
Bampton
P.A.
Andrews
J.M.
Tan
P.K.
Croft
A.
et al
Serious infections in patients with inflammatory bowel disease receiving anti-tumor-necrosis-factor-alpha therapy: an Australian and New Zealand experience
J Gastroenterol Hepatol
 
25
2010
1732
1738
12
Rahier
J.F.
Ben-Horin
S.
Chowers
Y.
Colon
C.
De Munter
P.
D'Haens
G.
et al
European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease
J Crohns Colitis
 
3
2009
47
91
13
Naganuma
M.
Kunisaki
R.
Yoshimura
N.
Nagahori
M.
Yamamoto
H.
Kimura
Y.
et al
Conception and pregnancy outcome in women with inflammatory bowel disease: a multicentre study from Japan
J Crohns Colitis
 
5
2011
317
323
14
Yang
Z.F.
Zhan
Y.Q.
Chen
R.C.
Zhou
R.
Wang
Y.T.
Luo
Y.
et al
A prospective comparison of the epidemiological and clinical characteristics of pandemic (H1N1) 2009 influenza A influenza virus and seasonal influenza A viruses in Guangzhou, South China in 2009
Jpn J Infect Dis
 
65
2012
208
214
15
Broor
S.
Krishnan
A.
Roy
D.S.
Dhakad
S.
Kaushik
S.
Mir
M.A.
et al
Dynamic patterns of circulating seasonal and pandemic A (H1N1) pdm09 influenza viruses from 2007–2010 in and around Delhi, India
PLoS One
 
7
2012
e29129
16
Rajatonirina
S.
Heraud
J.M.
Orelle
A.
Randrianasolo
L.
Razanajatovo
N.
Rajaona
Y.R.
et al
The spread of influenza A (H1N1) pdm09 virus in Madagascar described by a sentinel surveillance network
PLoS One
 
7
2012
e37067
17
WHO
Wkly Epidemiol Rec
 
84
2009
249
260
18
Takayama
K.
Kuramochi
J.
Oinuma
T.
Kaneko
H.
Kurasawa
S.
Yasui
M.
et al
Clinical features of 2009 swine-origin influenza A (H1N1) outbreak in Japan
Infect Chemother
 
17
2011
401
406
19
Hancock
K.
Veguilla
V.
Lu
X.
Zhong
W.
Butler
E.N.
Sun
H.
et al
Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus
N Eng J Med
 
361
2009
1945
1952
20
Belongia
E.A.
Irving
S.A.
Waring
S.C.
Coleman
L.A.
Meece
J.K.
Vandermause
M.
et al
Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1), 2008–2009 (H1N1), and 2007–2008 (H3N2) infections
JAMA
 
304
2010
1091
1098
21
Rahier
J.F.
Papay
P.
Salleron
J.
Sebastian
S.
Ellul
P.
Teich
N.
et al
Influenza A (H1N1)v infection in patients with inflammatory bowel disease: a case series
Aliment Pharmacol Ther
 
33
2011
499
500
Figure 1

H1N1 influenza virus infection in patients with IBD (n = 38). Patients whose ages were < 20 years were more frequently affected with H1N1 influenza infections than other age groups.

Figure 1

H1N1 influenza virus infection in patients with IBD (n = 38). Patients whose ages were < 20 years were more frequently affected with H1N1 influenza infections than other age groups.

Figure 2

Distribution of H1N1 influenza infections among age groups (15–19, 20–29, 30–39, 40–49, 50 ≦ years-old ) in IBD patients and general population. This was cited from a report from the Japanese Infectious Disease Surveillance Center. Patients or children aged < 15 were excluded in the figure.

Figure 2

Distribution of H1N1 influenza infections among age groups (15–19, 20–29, 30–39, 40–49, 50 ≦ years-old ) in IBD patients and general population. This was cited from a report from the Japanese Infectious Disease Surveillance Center. Patients or children aged < 15 were excluded in the figure.

Table 1

Clinical features of IBD patients.

  % (or range) 
Gender (male:female)  325:245  
Median age (range)  38.7 (14–82) 
Age groups (years) ≦ 19 45 7.9% 
 20–29 148 26.0% 
 30–39 155 27.2% 
 40–49 101 17.7% 
 50–59 59 10.4% 
 60 ≦ 61 10.7% 
IBD subtype UC 371 65.1% 
 CD 187 32.8% 
 Indeterminate colitis 12 2.1% 
Current smoking  83 14.6% 
Medication    
 Mesalamine/SASP 431 75.6% 
 Steroids 96 16.8% 
 Elemental diets 82 14.4% 
 Thiopurine 150 26.3% 
 Methotrexate 1.1% 
 Infliximab 81 14.2% 
 Tacrolimus 34 6.0% 
  % (or range) 
Gender (male:female)  325:245  
Median age (range)  38.7 (14–82) 
Age groups (years) ≦ 19 45 7.9% 
 20–29 148 26.0% 
 30–39 155 27.2% 
 40–49 101 17.7% 
 50–59 59 10.4% 
 60 ≦ 61 10.7% 
IBD subtype UC 371 65.1% 
 CD 187 32.8% 
 Indeterminate colitis 12 2.1% 
Current smoking  83 14.6% 
Medication    
 Mesalamine/SASP 431 75.6% 
 Steroids 96 16.8% 
 Elemental diets 82 14.4% 
 Thiopurine 150 26.3% 
 Methotrexate 1.1% 
 Infliximab 81 14.2% 
 Tacrolimus 34 6.0% 
Table 2

Risk factors for H1N1 influenza infections in IBD patients.

Univariate analysis 
 H1N1 influenza (+) H1N1 influenza (−) p value OR 95% CI 
(n = 38) (n = 76)    
Mean age (yrs) 30.0 +/− 13.2 30.7 +/− 13.2 0.79 – – 
Gender (male: female) 25:13 49:27 0.89 1.06 0.47–2.40 
Duration of disease (yrs) 6.3 +/− 6.4 7.8 +/− 6.7 0.36 – – 
Current smoking 2 (5.3%) 11(14.4%) 0.12 0.33 0.07–1.56 
Disease   0.71 1.17 0.51–2.70 
UC 26 50    
CD 12 26    
H1N1 influenza vaccinations 5 (13.2%) 12 (15.7%) 0.47 0.81 0.26–2.49 
Treatment      
5-ASA 31(81.6%) 58 (76.3%) 0.52 1.37 0.52–3.65 
Steroids 6 (15.8%) 16 (21.0%) 0.50 0.70 0.25–1.97 
Thiopurine 8 (21.0%) 23 (30.2%) 0.30 0.61 0.25–1.54 
Infliximab 6 (15.7%) 13 (17.1%) 0.86 0.91 0.31–2.61 
Any IM 22 (57.9%) 46 (60.5%) 0.78 0.90 0.41–1.98 
Any two IM 7 (18.4%) 17 (22.3%) 0.63 0.78 0.29–2.09 
Univariate analysis 
 H1N1 influenza (+) H1N1 influenza (−) p value OR 95% CI 
(n = 38) (n = 76)    
Mean age (yrs) 30.0 +/− 13.2 30.7 +/− 13.2 0.79 – – 
Gender (male: female) 25:13 49:27 0.89 1.06 0.47–2.40 
Duration of disease (yrs) 6.3 +/− 6.4 7.8 +/− 6.7 0.36 – – 
Current smoking 2 (5.3%) 11(14.4%) 0.12 0.33 0.07–1.56 
Disease   0.71 1.17 0.51–2.70 
UC 26 50    
CD 12 26    
H1N1 influenza vaccinations 5 (13.2%) 12 (15.7%) 0.47 0.81 0.26–2.49 
Treatment      
5-ASA 31(81.6%) 58 (76.3%) 0.52 1.37 0.52–3.65 
Steroids 6 (15.8%) 16 (21.0%) 0.50 0.70 0.25–1.97 
Thiopurine 8 (21.0%) 23 (30.2%) 0.30 0.61 0.25–1.54 
Infliximab 6 (15.7%) 13 (17.1%) 0.86 0.91 0.31–2.61 
Any IM 22 (57.9%) 46 (60.5%) 0.78 0.90 0.41–1.98 
Any two IM 7 (18.4%) 17 (22.3%) 0.63 0.78 0.29–2.09 

IM: Immunomodulators included any use of steroids, thiopurine, infliximab, tacrolimus, or methotrexate.

Table 3

Duration of H1N1 influenza symptoms and rate of use of antiviral treatments.

 Duration of influenza symptoms Need for antiviral treatments 
< 7 days ≧ 8 days or 8 days ≦ (−) (+) 
(n = 29) (n = 7) (n = 17) (n = 20) 
Mean age (years) 28.8 +/− 12.4 31.4 +/− 8.1 28.1 +/− 10.2 29.7 +/− 13.1 
Use of any IM 18 (62%) 3 (43%) 11 (65%) 11 (55%) 
 Duration of influenza symptoms Need for antiviral treatments 
< 7 days ≧ 8 days or 8 days ≦ (−) (+) 
(n = 29) (n = 7) (n = 17) (n = 20) 
Mean age (years) 28.8 +/− 12.4 31.4 +/− 8.1 28.1 +/− 10.2 29.7 +/− 13.1 
Use of any IM 18 (62%) 3 (43%) 11 (65%) 11 (55%) 

IM: immunomodulators.

Information regarding both duration of influenza symptoms in 2 patients and that regarding need for antiviral treatment was lacking in a patient.