The 2009 H1N1 influenza pandemic occurred in Wisconsin as 2 distinct waves during the first year of virus circulation. Wave 1 was driven by an intense outbreak in Milwaukee, where rates of hospitalization, ICU admission, and death were 7–15-fold greater than elsewhere in Wisconsin. We found that children aged <18 years and members of racial and ethnic minorities were disproportionately affected during wave 1, with the highest hospitalization rates observed among non-Hispanic black, Hispanic, and Asian Milwaukee residents. In contrast, the impact of wave 2 was experienced broadly and associated with 4-fold more hospitalizations and 5-fold more deaths statewide than during wave 1. Hospitalization rates during wave 2 remained higher in Milwaukee and among members of racial and ethnic minority groups. However, the subpopulations most severely affected during wave 1 in Milwaukee, particularly patients aged <18 years and black patients, experienced relatively reduced hospitalization rates during wave 2. Accordingly, frequencies of underlying conditions highly associated with specific ages, races, or ethnicities, particularly COPD and hematologic conditions, were significantly different between waves 1 and 2.
The successive waves of pandemic H1N1 infection in Wisconsin resembled those observed during the 1918 and 1968 pandemics, when second waves were associated with higher rates of morbidity and mortality than first waves [7
]. Evidence that the pandemic H1N1 virus was genetically stable, with no increased virulence between waves 1 and 2 [10
], suggests that the increased magnitude of wave 2 was attributable to broader geographic spread of pandemic H1N1 to immunologically naive populations throughout Wisconsin. In contrast to relatively limited geographic spread of pandemic H1N1 in wave 1 that occurred during warm weather and as the school year ended, the broader geographic spread during wave 2 may partially be related to colder temperatures and more time for widespread transmission to occur in schools, factors previously noted to increase influenza virus transmission [11
Although we observed extensive spread of pandemic H1N1 throughout Wisconsin during wave 2, hospitalization and mortality rates within Milwaukee remained disproportionately greater than in other Wisconsin areas during both waves. These findings resemble those during the 1918 influenza pandemic, when higher mortality rates were observed among urban populations compared with rural populations [13
]. A possible contributing factor is Milwaukee's high proportion of racial and ethnic minority residents, who are more likely than white residents to reside in densely populated areas, to have lower socioeconomic status, and to have medical conditions that are risk factors for complications from seasonal influenza [15
]. The hospitalization rate among Milwaukee's white residents was much lower than rates among racial and ethnic minority residents, particularly during wave 1. This disparity might also reflect patterns of social mixing, because Milwaukee is among the most segregated large metropolitan areas for blacks and Hispanics in the United States [18
Minority populations that were severely affected during wave 1 likely developed high levels of infection-acquired immunity, which consequently provided some degree of protection during wave 2. Accordingly, although hospitalization rates among white Milwaukee residents increased 2.5-fold from wave 1 to wave 2, rates remained constant among Hispanic Milwaukee residents and decreased significantly among black Milwaukee residents. Similarly, during the 1918 pandemic, army camps comprising troops exposed during the first wave had significantly lower rates of clinical illness and mortality during the second wave, compared with camps with higher proportions of previously unexposed troops [19
In Wisconsin, hospitalization rates among black, Hispanic, Asian, and American Indian/Alaskan Native residents were substantially greater than among white residents. These disparities occurred during both waves and were not restricted to urban Milwaukee; they were found throughout Wisconsin and much of the United States [20
]. Studies suggest that racial, ethnic, and socioeconomic disparities in mortality also occurred during the 1918 pandemic [23
], demonstrating a need for additional study regarding origins of these disparities. Regardless of cause, these findings underscore the importance of promoting influenza vaccination among racial and ethnic minority populations, particularly considering evidence that these groups have lower rates of vaccination against seasonal influenza [24
Planning for continued pandemic H1N1 transmission and for future influenza pandemics should consider the vulnerability of immunologically naive urban and rural populations. To identify these populations, surveillance systems must provide sufficient coverage and geographic detail to detect local and regional outbreaks and changes in influenza activity. Identifying communities and subpopulations that escaped substantial impact during a pandemic wave should be as important to public health planning as identifying those that were severely affected.
In Wisconsin and elsewhere, the 2009 H1N1 pandemic disproportionately affected children [2
]. Children are important drivers of influenza virus transmission and were found to be highly susceptible to pandemic H1N1 infection, compared with older persons, particularly those aged >
65 years, many of whom might have had partial immunity related to exposure to previously circulating influenza viruses [27
]. We also noted that the disease burden in Wisconsin among these older populations varied geographically and temporally, similar to characteristics of the 1918 pandemic in 2 Mexican cities [29
]. Although children had the highest hospitalization rates in Wisconsin during both waves, hospitalization rates among older persons significantly increased during wave 2. This trend resembles those noted during successive waves in previous influenza pandemics [30
] and, coupled with increased case-fatality ratios associated with pandemic H1N1 infection among older age groups, reinforces the need for sustained vaccination efforts targeting all age groups [3
Older patients also had a higher prevalence of underlying conditions and thus were more likely to experience more severe illness. Wave 2 in Wisconsin was associated with a dramatic increase in the presence of COPD as an underlying condition among hospitalized patients, a condition generally affecting adults [31
]. This increase likely was partially attributable to the increased proportion of older patients among those hospitalized during wave 2 and to other seasonal effects resulting in hospitalization among patients with COPD. This was also shown in our multivariate logistic regression model, in which the difference in COPD frequency between waves became statistically nonsignificant, likely revealing confounding by the change in age distribution. Although increased proportions of older patients and hospitalized patients with COPD should have resulted in higher proportions of severe outcomes during wave 2, these potential effects were countered by improved treatment, including increased proportions of patients aged ≥50 years receiving antiviral treatment and decreased times to hospitalization and receipt of treatment. In addition, improved treatment likely resulted in significantly improved outcomes involving ARDS among children and specific race or ethnicity groups.
Our study has several limitations. Because we used hospitalizations as the primary measure of the impact of pandemic H1N1 infection, and hospitals in Wisconsin vary in size, resources, case load, and influenza screening and hospitalization practices, some differences in rates according to geographic region, age, or racial or ethnic group might reflect differences between hospitals. In addition, because our data were limited to hospitalized patients, we were unable to conduct analyses and draw conclusions for the entire infected population, specifically regarding hospitalization and death rates. Also, without complete obesity and smoking data for all patients, we could not accurately estimate the prevalence of these factors or their association with disease severity. Furthermore, we were unable to obtain data regarding patient socioeconomic status, insurance type, or other information that could have enhanced our understanding of the demographic disparities identified in this analysis. Finally, our study describes the unique experience within Wisconsin, which was severely affected during both pandemic waves and experienced substantial geographic variation in impacts of the pandemic. Thus, our results might not apply to all areas.
Our study also has substantial strengths. Because we included all reported pandemic H1N1 hospitalizations during both waves in Wisconsin, we could calculate population-based hospitalization rates and describe geographic and demographic variations in disease incidence. In addition, consistent surveillance methods were used throughout the state of Wisconsin during the entire study period. This surveillance was strengthened by a WDPH recommendation to test all hospitalized patients with suspected influenza for pandemic H1N1 infection and by the availability of free RT-PCR confirmatory testing at Wisconsin public health laboratories, standardized case reporting, and an electronic, World Wide Web–based disease surveillance system that local health officials, hospital staff, and laboratories used to directly report cases. Also, regular communication by WDPH staff with Wisconsin local health departments and acute care hospitals resulted in consistent ascertainment of cases. Together, these efforts minimized detection bias and permitted us to accurately compare data from both waves.
Whether continued transmission of pandemic H1N1 will be associated with another wave of infection or with more typical seasonal transmission is currently unknown. Nonetheless, the disproportionate effect of pandemic H1N1 infection on many groups and regions in Wisconsin during both waves underscores the need to vigorously promote vaccination among all populations. In addition, because of the changing characteristics and impacts of successive influenza pandemic waves, comprehensive surveillance is necessary to guide influenza vaccination efforts and pandemic response planning, thereby reducing the morbidity and mortality associated with 2009 H1N1 and future influenza pandemics.