An investigation of IPD cases in Denver during October 2009 showed 3× the average number of IPD cases identified during October of the previous 5 years and a notable association with pandemic (H1N1) 2009 virus infection. Our findings do not prove a causal relationship between pandemic (H1N1) 2009 and IPD. However, we confirmed that 10 (17%) of 58 case-patients had influenza, and 2 estimates of the maximum proportion of IPD cases that may have been associated with pandemic (H1N1) 2009 showed that proportion was 52%–62%. Increases in testing for pneumococcal infection were modest and could not account for the magnitude of the increase in IPD incidence that we observed. However, the reported increase by area clinical laboratories in blood culture positivity for pneumococci supports a true increase in IPD incidence.
This investigation highlighted factors that may be distinct to IPD cases associated with pandemic (H1N1) 2009. Previous influenza pandemics have implicated secondary bacterial infection as a complication and cause of serious illness and death (1
). These studies were based largely on autopsy series and histologic confirmation, but were limited in their ability to evaluate clinical presentation, symptoms, and onset that may be distinct to IPD cases identified during nonpandemic influenza seasons.
During the 2009–10 influenza season, the predominant circulating influenza virus was pandemic (H1N1) 2009 virus (11
). IPD cases mirrored the epidemiology of pandemic (H1N1) 2009, peaked at the same time, and affected younger persons. Because some cases of IPD occur every October and because some cases of IPD are likely attributable to seasonal influenza (12
), we compared cases detected during October 2009 with IPD cases seen during a peak month of seasonal influenza activity. Attack rates for pandemic (H1N1) 2009 were likely higher than those for seasonal influenza (H1N1) (13
). Thus, the October IPD cases were more likely to mirror the epidemiology of pandemic (H1N1) 2009.
Studies in animal models demonstrated that influenza strains during previous pandemics have different abilities to predispose persons to secondary pneumococcal infections (14
). If pandemic (H1N1) 2009 contributed to the increase in IPD cases during October 2009, we would expect a shift from the baseline IPD epidemiology toward a younger population with conditions known to increase the risk for infection with pandemic (H1N1) 2009 virus. In addition, the prevalence of underlying conditions (especially chronic lung disease) is consistent with a causal association between pandemic (H1N1) 2009 and October 2009 IPD cases.
October 2009 cases were not more severe than February 2009 cases, although our statistical power to identify a significant difference was limited. However, for persons 20–39 years of age, a high proportion of IPD hospital admissions required ICU (there were no prepandemic data for comparison). Data gathered during the pandemic from domestic and international sites (4,15,16
) suggested that pandemic (H1N1) 2009–associated IPD was not unique to Denver. However, there were no widespread levels of IPD that were greater than expected. At the time of our investigation in Denver, whether increases in IPD in other ABCs sites were statistically or epidemiologically significant was not clear. Since that time, increases have become apparent in other sites, although these increases were consistently more modest than those observed in Denver and were not as thoroughly investigated. In contrast to the previous 5 years, Denver experienced a peak in IPD in October 2009, which was likely attributable to pandemic (H1N1) 2009, and a second peak in December, which likely represented endemic disease.
Prevention of IPD during future influenza pandemics should focus on vaccination and prompt diagnosis. This influenza pandemic was the first in which pneumococcal vaccines and antiviral drug treatment were available. Among adults with IPD in Denver, vaccination rates for persons 18–64 years of age with indications for vaccination were less than the national rate, and vaccination rates for persons >65 years of age were similar to national estimates (17
). The increase in IPD cases during October, the peak month of hospitalizations of persons with pandemic (H1N1) 2009, might have been minimized if adults at highest risk for IPD had received the recommended polysaccharide vaccine. Increasing PPV23 coverage in populations with increased risk for IPD is a key prevention measure, especially in anticipation of influenza pandemics.
Introduction of PCV7 into routine childhood immunization programs in the United States resulted in dramatic reductions in rates of pneumococcal-related diseases and major changes in the epidemiology for all age groups (5,18–23
). In Denver during October 2009, we identified only 2 cases of IPD caused by serotypes included in PCV7, both in adults.
Whether vaccine against pandemic (H1N1 2009, which became available in Denver during late October, could have reduced the number of pandemic (H1N1) 2009–associated IPD cases is unknown. Antiviral drug administration was sometimes delayed or withheld despite national guidance for treatment even if >48 hours had elapsed from onset of illness (24
), and such withholding may have changed the clinical course of some of the IPD cases.
Outbreaks of S
have occurred in many settings (25–39
), and individual serotypes have been implicated in localized outbreaks (27–29,31,39
). The variety of serotypes identified in this outbreak indicates that the increase in IPD was not attributable to enhanced transmission of a single serotype. To address whether the increase in October 2009 reflected a clonal outbreak of 7F, we analyzed the proportion of IPD cases in Denver that were serotype 7F during 2004–2010. During 2004–2009, the proportion of 7F increased (from 3% to 25%). When we evaluated all months except October during 2004–2009, the proportion of 7F still increased (from 2% to 23%). The proportion of IPD caused by 7F has been increasing in Denver over time and cannot be attributed to an increase in October 2009 alone or the pandemic. Furthermore, the distribution of serotypes was similar to serotype distributions in national (5
) and Denver-specific IPD cases, which suggested that if pandemic (H1N1) 2009, was causally associated with this outbreak, it facilitated pneumococcal infection without a predilection for any particular serotype.
Our investigation had limitations. Low numbers of cases may have limited our ability to identify differences in the epidemiology of IPD during October 2009 and peak months of seasonal influenza activity. We were also unable to ascertain PPV23 vaccination histories for all cases, which may have underestimated PPV23 use. Of 47 influenza tests ordered, 9 (19%) were only rapid tests. The sensitivity of rapid tests for detecting pandemic (H1N1) 2009 ranged from 20% to 40% (40
). Twenty-four (41%) of 58 IPD case-patients were not tested for pandemic (H1N1) 2009 by PCR (the standard for detection), which may have underestimated the number of confirmed influenza-associated IPD cases. Some patients with negative test results may have been infected with influenza virus but were tested too late in the course of their illness. Finally, ILI does not capture all influenza cases and cases with influenza within 5 days of pneumococcal culture and not tested samples would not be included for a possible influenza-associated IPD case. In addition, ILI includes symptoms that occur frequently with signs and symptoms of pneumococcal pneumonia and may be a result of the symptom course of IPD rather than preceding influenza infection.
In conclusion, up to two thirds of IPD cases in Denver during October 2009 may have been associated with pandemic (H1N1) 2009. Pandemic influenza may have altered the epidemiology of IPD and shifted the age distribution to younger persons and to persons 18–64 years of age with an increased prevalence of underlying conditions. Missed opportunities for PPV23 vaccination were common. During future influenza pandemics, public health officials should increase awareness of the association between IPD and influenza among persons of greatest risk for influenza-associated IPD. Prevention efforts should include use of pneumococcal vaccines and vaccines for directly preventing influenza infection.