Epidemiology of Influenza-like Illness during Pandemic (H1N1) 2009, New South Wales, Australia

To rapidly describe the epidemiology of influenza-like illness (ILI) during the 2009 winter epidemic of pandemic (H1N1) 2009 virus in New South Wales, Australia, we used results of a continuous population health survey. During July–September 2009, ILI was experienced by 23% of the population. Among these persons, 51% were unable to undertake normal duties for <3 days, 55% sought care at a general practice, and 5% went to a hospital. Factors independently associated with ILI were younger age, daily smoking, and obesity. Effectiveness of prepandemic seasonal vaccine was ≈20%. The high prevalence of risk factors associated with a substantially increased risk for ILI deserves greater recognition.

D uring winter 2009, Australia experienced a strong infl uenza epidemic, caused by the pandemic (H1N1) 2009 virus. In New South Wales (NSW), the most populous state of Australia (≈7 million persons), the epidemic lasted from late June through early September (1). Despite intense surveillance and response efforts, determining the epidemiology of infl uenza at the whole-population level remains diffi cult, and considerable uncertainty about the disease remains because only a small proportion of infected persons are tested (2).
Survey methods have been infrequently used to assess the epidemiology of pandemic infl uenza virus infection in the general population. In 1919, a personal household interview survey using a sample of population census districts from large population centers was used to assess illness associated with the fi rst wave of pandemic infl uenza in the Unites States. Persons called intelligent inspectors determined whether the household member was "sick since September 1, 1918, with infl uenza, pneumonia, or indefi nitely diagnosed illness suspected to be infl uenza." The survey demonstrated substantial demographic, geographic, and socioeconomic variation in the apparent attack rate of infl uenza. Expressed as a percentage, the overall incidence rate of clinical infection was estimated to be ≈28% during the fi rst wave. The incidence rate was ≈35% in children and declined with age to ≈30% in adults <35 years of age and to ≈10% in persons >75 years of age. Incidence was higher among women 15-35 years of age than among men in the same age group (3,4).
During the fi rst epidemic wave of pandemic (H1N1) 2009, we used a continuous population health survey to better understand the epidemiology of the infl uenza (H1N1) virus in the general community. This situation also created an unprecedented opportunity to assess the prevalence of seasonal infl uenza vaccination among persons of all age groups in our population and its effectiveness against ILI during pandemic (H1N1) 2009.

Methods
Since 2002, the NSW Population Health Survey has been operating continuously to provide monthly estimates of health status and risk factors. The survey involves computer-assisted telephone interviews of a randomly selected member of randomly selected households. The target population is state residents in private households with private telephones. The sample is selected by using telephone number ranges obtained from an electronic telephone book that has been geocoded (spatial coordinates assigned to addresses) and stratifi ed by 8 regional health Epidemiology of Infl uenza-like Illness during Pandemic (H1N1) 2009, New South Wales, Australia service boundaries within the state. List-assisted randomdigit dialing is then used to contact households. The target sample is ≈1,500 persons per regional health service per year, which equals 12,000 persons per year for the state. The survey covers all age groups, and interviews for children <16 years of age are reported by a parent or caregiver. Full details of sample selection and procedures are provided by Barr et al. (5). The survey has been approved by the NSW Population Health and Health Services Research Ethics Committee.
When circulation of pandemic (H1N1) 2009 virus in NSW became apparent, ethics approval was obtained to add supplementary questions to the survey to determine the incidence of infl uenza-like illness in the population and associated health care-seeking behavior and absence from normal duties; these questions were added on July 19, 2009. The questions were as follows: "In the last 4 weeks, did you have an illness with any of the following symptoms: fever or high temperature, cough, sore throat, runny nose, fatigue, chills or shakes, body aches and pains, shortness of breath, the fl u or fl u-like symptoms?" Responses were recorded for each sign or symptom. Respondents answering "yes" to any sign or symptom were asked the following: "Did you see a GP for this illness?"; "Did you go to a hospital or emergency department for this illness?"; and "How many days were you unable to work, study, or manage day-today activities because of the illness?" At the same time, we extended the age range for respondents routinely asked whether they had been "vaccinated or immunized against fl u in the past 12 months" to persons >6 months of age. Previously, the question had been asked only of persons >50 years of age. The extended age range would enable assessment of vaccine effectiveness against ILI. We defi ned ILI as self-reported fever or high temperature with cough and fatigue. In a range of general practice surveillance systems for seasonal infl uenza in Australia, this defi nition performed better than alternative defi nitions; positive predictive value was 23%-60% and negative predictive value was 64%-91% (6).
To obtain monthly estimates of ILI incidence, for any respondents reporting a symptom in the past 4 weeks we assigned their illness to the middle of the reference period, that is, 14 days before the interview date. This illness date was then assigned to a month of illness.
Answers to other questions routinely asked in the survey enabled analysis of additional factors that might be associated with ILI reporting (7), including age (0-15, 16-34, 35-49, 50-64, or >65 years); sex; household size (1-2 or >3 residents); number of children in household (<2 or >2); urban or rural location of residence; socioeconomic disadvantage at respondent's residential postal code, which is derived from the Australian Census and takes into account income, education, occupation, employment status, indigenous status, housing, and other variables (index of relative socioeconomic disadvantage [8]: lowest 2 quintiles = disadvantaged and upper 3 quintiles = not disadvantaged); current asthma (respondents >2 years of age, diagnosis made by a doctor, and symptoms or treatment in the past 12 months); nongestational diabetes or high blood glucose status (>9 years, diagnosis made by a doctor); smoking status of persons >16 years of age (daily smoker, occasional smoker, ex-smoker, or nonsmoker); body mass index ([BMI] [weight in kilograms]/[height in meters] 2 ) of persons >2 years of age (>30 = obese, 25 to <30 = overweight, and <25 = healthy or underweight); alcohol drinking at levels associated with health risk (>2 Australian standard drinks [1 standard drink = 10 g alcohol] on any day) (9); adequate physical activity for persons >16 years of age (at least 150 minutes exercising per week on >5 occasions, adequate or not adequate), psychological distress score for persons >16 years of age (Kessler-10 scale ( [10] high or very high [score >22], moderate, or low); and vaccinated against pneumococcal disease in the past 5 years for persons >50 years of age (yes or no).
As is standard for household population surveys, the data record for each survey respondent was assigned a numeric weighting, which was used in all analyses to scale their results to the total NSW population. The weighting value takes into account the probability (by age, sex, and geographic region) of being selected for participation in the survey (5). Regression models were used to obtain the relative risk (RR) of reporting ILI for each of the factors listed in the previous paragraph. The dependent variable for each model was ILI, which was assigned 1 of 2 values: 1 if the respondent met the criteria for ILI and 0 otherwise. The independent variables were >1 factor.
Our modeling strategy was to individually test the association between each factor and ILI by using a regression model and then to develop a fi nal model incorporating multiple factors to assess whether independent associations remained. Because age was strongly associated with ILI, we included it as an independent variable in the model for all single-factor assessments. Factors with p<0.1 for an individual association were included in the fi nal model. Despite its nonsignifi cance, sex was included in the fi nal model because the prevalence of risk factors in our population was known to differ by sex.
To estimate RRs from survey data instead of the more usual odds ratios, we used Poisson regression analysis with robust variance estimation. RRs were calculated by using the GENMOD procedure included in SAS Statistical Analysis Software version 9.1.3 for Windows (Cary, NC, USA) with the following programming statements: a model statement with options dist = Poisson and link = log; a class statement including the unique survey respondent number variable; a repeated statement with an independent correlation structure (corr = ind) and specifying the unique survey respondent number variable as the subject parameter; and a weight statement specifying the respondent sample weighting normalized to sum to the total sample size (11)(12)(13). Because the Poisson model uses the natural logarithm as the link function, exponentiation of the parameter estimates was used to obtain the RR for the study factors.
Vaccine effectiveness for ILI was estimated by 1-RR. RR was the age-adjusted relative risk of reporting ILI among respondents reporting seasonal infl uenza vaccination in the past 12 months relative to that for unvaccinated respondents. RRs were obtained from the regression analysis (14).

Incidence of ILI
From July 19 through October 14, 2009, completed interviews were obtained from 2,909 respondents from 5,017 eligible households contacted during that period. Participation rate was 58.0%.

Prevalence of Seasonal Infl uenza Vaccination
When we calculated prevalence of seasonal infl uenza vaccination for all age groups, we found that one quarter (25%, 95% CI 23%-28%) had been vaccinated against infl uenza in the previous 12 months. The proportion was highest among persons >65 years of age (74%, 95% CI 71%-78%), fell to 33% (95% CI 29%-38%) among those 50-64 years, and was <20% among those <50 years (Table  4). Previous estimates in NSW were based on persons >50 years of age because national immunization policy focused on this age group.

Factors Associated with Reporting ILI
Younger age was strongly associated with ILI (Table  5), which was ≈6× more likely to be reported for children <15 years of age than for persons >65 years of age. Therefore, for evaluation of all other individual factors, we adjusted for age. Only obesity and daily smoking were positively associated with reporting ILI. All remaining factors showed no signifi cant association. In the fi nal regression model, we included age, sex, BMI, and smoking status. Although sex was not associated with ILI, obesity and smoking in our population varied substantially by sex and were included in the model. Only persons >16 years of age were included because 16 years was the youngest age for which smoking questions were asked. The association with younger age remained in the fi nal model (Table 6). Among the 13.0% (95% CI 10.8%-15.1%) of the population >16 years of age who reported daily smoking, the risk for ILI was 90% (95% CI 10%-226%) higher than that for less frequent smokers and nonsmokers combined. Among the 18.0% (95% CI 15.9%-20.1%) whose BMI was in the obese category, the risk for ILI was 132% (95% CI 30%-316%) greater than that for the combined group of persons whose BMI was healthy or underweight.

Effectiveness of Seasonal Infl uenza Vaccine
When the age-adjusted RR for ILI among persons reporting vaccination with the seasonal infl uenza vaccine in the past 12 months was used, the estimated vaccine effectiveness was 20.0% (95% CI -30.5% to 51.0%), indicating a possibly mild but nonsignifi cant benefi t. Analysis of effectiveness in specifi c age groups and by sex, region, smoking status, or obesity did not indicate any signifi cant benefi t (Table 7).

Discussion
In NSW, during the fi rst Southern Hemisphere winter in which pandemic (H1N1) 2009 virus was circulating, at least one quarter of the population and one third of children experienced ILI. Many infections other than infl uenza can cause ILI (15,16); however, this study was conducted during the peak months of the epidemic in NSW, when the predictive value of ILI for infl uenza infection would be optimal (6). The epidemic was recognized in Australia after mid-June and grew rapidly (1). We were able to obtain full monthly estimates of ILI from July only. Late June was part of the recall period of the survey questions for respondents interviewed in July, and some of that activity may have been included in the July estimate.
ILI incidence was similar in urban and rural regions and in each sex. Approximately half the persons who reported ILI had to limit their usual activities for <4 days. Approximately half sought care for their illness at a general practice, and 5% sought care at a hospital. Vaccination against seasonal infl uenza did not protect against ILI. Daily smoking and obesity each independently doubled the risk for ILI.
Consistent with the known epidemiology of pandemic (H1N1) 2009 virus infection (1,(17)(18)(19), incidence of ILI decreased with age; the decline was sharp for those >65 years of age. The age-specifi c estimates of ILI incidence in NSW in 2009 were remarkably similar to those reported during the 1918 infl uenza pandemic in the United States (4). Our overall estimate of an ILI rate of 23% was higher than the overall population infection rate for pandemic (H1N1) 2009 of 16% estimated by a recent seroprevalence study from NSW (20). Although the CIs of both estimates overlapped and thus the estimates did not differ signifi cantly, explanations for our higher estimate could be as follows: 1) some of the ILI in our study was caused by other infl uenza strains that circulated earlier in the season (1) and by pathogens other than infl uenza; 2) our study included information collected through the end of September, whereas the seroprevalence study included some specimens collected before the end of the epidemic ‡Because this category overlaps the 2 categories above, total is not 100%. Other studies that assessed household size and risk for transmission found mixed results: some found increased risk (21,22) and another found decreased risk (23) with increasing household size. A higher number of children in a household has also been identifi ed as a risk factor for infl uenza transmission in households (24). However, our fi nding of no association with either household size or number of children in the household is consistent with the result of household transmission studies of the pandemic 2009 (H1N1) virus (18,25) and with results of another study of ILI among children during seasonal infl uenza season in Australia (26). This lack of effect may refl ect improved living standards in this country.
The lack of protection from recent seasonal infl uenza vaccination has been reported elsewhere (18,27,28), but a study in Mexico found partial protection (29). The subtype H1N1 component of the Northern and Southern Hemisphere vaccines at that time was the same: A/Brisbane/59/2007-like. Obesity and smoking are 2 preventable risk factors we found to be strongly associated with ILI. Smoking has been frequently identifi ed as a risk factor for infl uenza; the identifi ed mechanisms are mechanical, structural, and immunity related (30)(31)(32). Although obesity has been frequently identifi ed as a risk factor for severe outcomes of infection with pandemic 2009 (H1N1) virus (33)(34)(35), it has not been previously recognized as a risk factor for susceptibility to symptomatic infl uenza infection in humans. A recent study in mice found that an immune memory response to recent infl uenza infection was reduced among obese mice; this reduced memory led to more severe disease, lung pathology, and virus titers after a second exposure to the same mouse-adapted infl uenza strain (36).
In addition to possibly excluding the early part of the epidemic, our study has other limitations. Infl uenza in respondents was not confi rmed by testing; other common winter respiratory viruses, such as respiratory syncytial virus, can cause a similar syndrome (16). General practice surveillance in various regions of Australia, conducted during circulation of seasonal infl uenza virus, indicated that the syndrome defi nition we used had a positive predictive value of 23%-60% (6). Although these values are not high, positive predictive value is probably increased during a larger than usual epidemic (37). Pandemic concern may have prompted more persons than usual to get vaccinated for seasonal infl uenza. This concern and response would produce higher vaccination prevalence in our study than would have occurred in the absence of a pandemic. Evidence shows that publicity prompted increased vaccination among persons >65 years of age, from 68% in April 2009 to 77% in May 2009. Prevalence remained higher for several months (38). In our study, we were unable to include 2 frequently reported risk factors for poor outcomes of pandemic (H1N1) 2009 virus infection: pregnancy and indigenous status (39,40). Although indigenous status is included in the health survey, the number of Aboriginal and pregnant respondents in the period of time covered would be too small to obtain usable estimates for these risk factors.

Conclusions
When pandemic (H1N1) 2009 virus was circulating in the NSW population, ILI was experienced by at least one quarter of the population. Recent prepandemic seasonal vaccination was not protective. Although smoking is already known to increase susceptibility to infl uenza infection, obesity is not. The role of obesity in susceptibility needs further evaluation in studies in which infl uenza infection can be confi rmed. The high prevalence of these preventable risk factors in our population, combined with a substantially increased risk for ILI, deserves greater recognition. Using an established health survey for monitoring ILI is *Influenza-like illness defined as fever with cough and fatigue. Some questions are only collected on selected age groups, so sample sizes vary. CI, confidence interval. †Not stated and "Don't know" responses were included in the reference category. Among parameters with any such responses, the proportions were body mass index 5.2%; smoking status 0.1%. ‡Statistically significant results at the 5% level are in boldface. inexpensive and provides an opportunity to assess a broad range of risk factors. Continued monitoring will enable better assessment of the value of survey-based infl uenza surveillance through comparison with other infl uenza and respiratory illness surveillance systems and can provide continuous assessment of risk factors for ILI.