All clinical laboratories report positive influenza test results to the Communicable Disease Control Directorate (CDCD), Department of Health, Western Australia. For diagnosis, respiratory samples, usually combined nose and throat swab specimens, were tested by PCR. More than 90% of the specimens were tested at PathWest Laboratory Medicine Western Australia, Queen Elizabeth II Medical Centre, by using an assay that identified and distinguished between pandemic (H1N1) 2009 and seasonal influenza A/H1, A/H3, and B (17); positive results for pandemic (H1N1) 2009 influenza virus reported from other clinical laboratories were considered as single infections with pandemic (H1N1) 2009.

Reports of all PCR-confirmed influenza infections were reviewed. Patients were excluded if the results could not differentiate between pandemic and seasonal viruses or if the patient was identified as infected with pandemic (H1N1) 2009 and seasonal influenza. Pandemic influenza was defined as PCR-confirmed pandemic (H1N1) 2009 influenza infection, and seasonal influenza was defined as any PCR-confirmed influenza infection for which infection with pandemic (H1N1) 2009 virus had been excluded.

The study began May 29, 2009 (1 week after the illness onset in the first person with confirmed pandemic [H1N1] 2009 influenza infection in Western Australia) and concluded August 7, 2009 (Figure 1) (18). From the study inception through July 13, 2009, attempts were made to interview every patient with confirmed influenza illness reported to CDCD. On July 14, 2009, we instituted a sampling framework because of increasing numbers of reported infections. The sampling scheme entailed identifying the last digit of a sequentially-assigned identification number from the first patient reported each day with seasonal or pandemic (H1N1) 2009 influenza, then selecting all patients reported that day with the same last digit. If <20 patients were identified for interview, we added 1 to the digit (n + 1) and selected additional patients by using the same procedure. This process was repeated until up to 20 persons with seasonal influenza and 20 with pandemic influenza were chosen each day. If <20 influenza infections were reported on a given day for either seasonal or pandemic (H1N1) 2009 influenza, we attempted to interview all patients reported on that day.

Study participants were interviewed by a trained nurse who used a standard questionnaire. If a patient was unable to answer questions or was <18 years of age, the nurse interviewed a parent or other family member familiar with the patient’s situation. We made 6 attempts to contact the patient or a proxy, after which the patient was considered not contactable. Diagnostic specimens of participating patients were collected a median of 2 d after illness onset (interquartile range [IQR] 1–3 d), and patients were interviewed a median of 6 d after onset (IQR 5–8 d).

The patient’s self-reported symptoms, treatment with antiviral medications, presence of underlying medical conditions, and disease disposition were recorded. Information on hospitalization was obtained at the time of the interview and by retrospectively querying a hospital discharge database that covers all public hospitals in the state and 1 major private metropolitan facility. A cross-check with the hospital discharge database was performed for every influenza notification received at CDCD.

For our analysis, we first characterized all patients with pandemic (H1N1) 2009 or seasonal influenza infection reported to CDCD during the study period (the target population) in terms of age, sex, and hospitalization status by using univariate Mantel-Haenszel χ² tests for proportions and t tests for population means. We then compared patients who were interviewed (the study population) with the remaining patients not interviewed in the target population in terms of age, sex, and hospitalization status; if a significant difference was identified, we weighted the interview responses from the study participants to reflect the target population (19). Finally, by using the data obtained during interviews, we performed univariate analyses to compare patients with pandemic influenza with those with seasonal influenza with respect to reported symptoms, underlying medical conditions, and treatment. Because the age structure of the population with pandemic influenza differed from that with seasonal influenza, we also computed odds ratios (ORs) for individual symptoms or underlying medical conditions by using logistic regression to control for age. In each of the regression analyses, the dependent variable was defined as influenza type (pandemic/seasonal), and the independent variables were limited to age in years and 1 dichotomous variable representing the presence or absence of a single patient characteristic (e.g., a symptom or underlying medical condition).

To assess whether antiviral medications might have influenced the symptoms reported, we performed a subanalysis restricted to patients who were treated with antiviral agents within the first 2 days of illness onset (early use of antiviral drugs) and compared those patients with patients who were never treated, controlling for age, influenza type, and the presence of underlying medical conditions.

Influenza-like illness was defined as documented fever >38°C or a history of fever when the temperature was not known, and cough or sore throat, or both. Risk difference was defined as the absolute difference in the proportion of pandemic and seasonal influenza patients reporting a given parameter. A p value <0.05 was considered significant. Statistical analyses were performed by using Epi Info 2000 (Centers for Disease Control and Prevention, Atlanta, GA, USA).

This comparison of >1,000 total confirmed seasonal and pandemic (H1N1) 2009 influenza infections occurring contemporaneously over the peak of the traditional influenza season yielded several findings. First, the spectrum of clinical illness due to pandemic influenza was similar to that caused by seasonal influenza. Although several symptoms were more common in patients with pandemic influenza, the differences were modest and of limited clinical importance.

Our findings generally parallel those from a recent comparative analysis in Singapore, with some differences. For example, in Singapore, the proportions of patients with seasonal and pandemic influenza who reported diarrhea were 0% and 4%, respectively; these figures are substantially lower than those found in our study (12% and 19%, respectively), despite the fact that in both settings most nonpandemic influenza viruses identified were influenza A (H3N2). These differences highlight the need to consider data from diverse geographic, cultural, and healthcare environments when characterizing the clinical manifestations of influenza.

Second, we observed that the hospitalization rates for pandemic (H1N1) 2009 and seasonal influenza infections were similar. Our ability to use a comprehensive statewide database to identify hospital admissions in the broader target population permitted a robust analysis that found the overall proportion of confirmed pandemic and seasonal illnesses hospitalized was not significantly different when aggregated data were used in univariate analyses (p>0.05). However, if the analysis was controlled for age, the odds of being hospitalized were significantly greater for the population with pandemic influenza. These seemingly dissonant results actually reflect the fact that for many age groups there was a higher risk for hospitalization with pandemic (H1N1) 2009, but because patients with seasonal influenza were older relative to those with pandemic influenza and elderly patients are more likely to be admitted to hospital when ill with influenza, the cumulative hospitalization rate in the 2 patient groups was similar.

In addition, in this study, the mean duration of hospitalization was not statistically different between patients with pandemic (H1N1) 2009 and seasonal influenza even though other indicators suggested pandemic patients were hospitalized for longer periods. An analysis of a larger sample of hospitalized patients is underway.

Third, the underlying medical conditions associated with pandemic (H1N1) 2009 and seasonal influenza illnesses diagnosed in the community were nearly identical in terms of the type and number of conditions reported. Most patients in both groups reported no risk factors, and only when we controlled for age did we find an association between having >1 underlying medical condition and pandemic influenza. Notably, the largest risk difference we observed was for was pregnancy (4%). Univariate analyses showed that the association between pregnancy and pandemic influenza approached statistical significance (p = 0.08; analysis not shown). When we restricted our analysis to women 15–45 years of age, the risk difference nearly doubled, but significance was still not attained, perhaps as a consequence of the smaller sample size. Seasonal influenza is a well-established cause of serious illness during pregnancy, and several reports indicate that the risk for severe illness from pandemic (H1N1) 2009 may be even greater (20–23).

Obesity, newly recognized as a risk factor for severe influenza illness during the 2009 pandemic, was reported as often by patients with seasonal influenza as by those with pandemic influenza (11% vs. 9%; p>0.05). This finding suggests that obesity may be equally important as a risk factor for seasonal and pandemic (H1N1) 2009 (24).

Finally, because our study was not a randomized controlled trial, inferences about the effect of antiviral medications should be viewed with caution. For example, our observation that antiviral drug use was negatively associated with reported rhinorrhea may be due to the effect of treatment or may have resulted from a relative disinclination of providers to prescribe antiviral drugs for patients with rhinorrhea, on the basis of an assumption that nasal symptoms make influenza infection less likely (25). However, the robust positive association we observed in our population between antiviral agent use and nausea/vomiting suggests that there was a causal relationship, a conclusion consistent with that of a recent metaanalysis on oseltamivir use (26).

The limitations of our study include the following: reported underlying medical conditions were not objectively verified, data on the duration of symptoms were not collected, and interviewers were not blinded to influenza type when administering the questionnaire. Also, because this was a public health evaluation of notified influenza infections principally detected through routine healthcare practices in the community at large, we were unable to control for potential biases stemming from who was tested and who was not. However, because the healthcare provider could not be confident of whether the patient had pandemic (H1N1) 2009 or seasonal influenza at the time of testing, any bias in who was selected for testing should be approximately equal for pandemic (H1N1) 2009 and seasonal influenza patient groups. Lastly, a limitation inherent in the case–control study design we used was that we are unable to assess the extent to which the underlying medical conditions reported increased the risk for a diagnosis of influenza of either type, when compared with persons without underlying medical conditions.

In summary, our head-to-head comparison of confirmed pandemic (H1N1) 2009 and contemporaneous seasonal influenza infections found little to differentiate the 2 in terms of symptoms, underlying medical conditions, and the proportion of patients hospitalized. These results add to the growing body of knowledge about pandemic (H1N1) 2009 and are in general agreement with several studies that used different methods in other settings (27). These data are important because early in the pandemic some reports espoused different conclusions; 1 report estimated the lethality of pandemic (H1N1) 2009 to be ≈1 death per 10,000 infections, about 100× greater than that for regular seasonal influenza (28,29). Worldwide, unprecedented levels of resources have been expended to mitigate the impact of pandemic (H1N1) 2009. In the United States alone, the federal government appropriated $7.65 billion for this effort (30). This commitment to controlling pandemic (H1N1) 2009 is to be lauded, but we must not lose sight of the fact that seasonal influenza remains an important, albeit relatively uncelebrated, cause of illness and death each year. As the pandemic (H1N1) 2009 response draws to a close, it may be prudent to revisit the level of effort directed toward reducing the enormous effects, in terms of costs and health outcomes, associated with annually recurring influenza epidemics (31).