We identified 121 cases of invasive H. influenzae in Utah adults reported to the UDoH during 1998–2008 (Table). The incidence of H. influenzae invasive disease was 0.66 cases per 100,000 person-years averaged over the 11 years. Incidence increased over the study period from 0.14 cases per 100,000 person-years in 1998 to a peak in 2008 of 1.61 cases per 100,000 person-years (p = 0.0023, by linear test for trend) (Figure 1). We observed a marked seasonality with winter predominance: 41.3% of cases occurring in winter, 26.4% in spring, 21.4% in fall, and 10.7% in summer. We observed no significant difference in distribution between sexes, with 64 cases in women and 57 cases in men (p = 0.65).

The incidence rates estimated by using the IH data showed a similar trend (Figure 1). We identified 94 cases of invasive H. influenzae, with an estimated average annual incidence of 1.05/100,000 person-years. The incidence increased from 0.54/100,000 person-years in 1999 to 1.27/100,000 person-years in 2008 (p = 0.002, by linear test for trend). Although the estimated rates differed, the trend in increasing incidence was similar for both data sources.

The incidence of invasive disease was markedly higher among persons >65 years of age; the average incidence in this age group was 2.74 cases per 100,000 person-years and increased to 6.14 cases per 100,000 in 2008. The average incidence for persons 18–34, 35–49, and 50–64 years of age were 0.25, 0.26, and 0.88 per 100,000 person-years, respectively. Compared with persons 18–34 years of age, patients >65 years of age had a 12-fold greater risk for invasive disease (risk ratio 12.5, 95% confidence interval [CI] 7.29–21.32; p<0.0001). The incidence of invasive disease increased significantly over the study period among those >65 years of age (Figure 2).

Despite the virtual elimination of Hib in areas with widespread use of Hib vaccine, invasive disease caused by H. influenzae remains a major source of illness and death. The incidence of invasive H. influenzae in Utah adults appears to be increasing; most of the increase in H. influenzae disease incidence was attributable to an increase in nontypeable and Hif strains. We found that invasive H. influenzae disease was most common in persons >65 years of age and was associated with a high mortality rate.

The overall incidence of invasive H. influenzae disease in adults in our population, 0.66 cases per 100,000 person-years, was similar to rates observed in Illinois (1.0/100,000 person-years in 1994) (7) and slightly lower than rates among Alaskans during 1991–1996 (1.4/100,000 person-years) (5). We found a significant increase in the incidence of invasive H. influenzae over the study period by using 2 surveillance methods. Several studies in addition to ours suggest an increase in invasive disease caused by to non-type b H. influenzae among adults (5,7,13). The reasons for this change are unclear, and might reflect changes in the organisms, changes in the number of persons at high risk, or perhaps waning of cross-immunity induced by exposure to Hib.

As the prevalence of Hib has decreased, other encapsulated serotypes seem to have emerged as major causes of invasive disease, including Hif in Illinois and Hia in Brazil, Manitoba, and Northwestern Ontario (7,10,14,15). Similar to findings in Illinois, Hif was the second most common serotype in our analysis (25%), and cases of invasive Hif contributed substantially to the increase of invasive H. influenzae cases we observed in 2007–2008. Although Hia was the third most common isolate among adults in our study, it accounted for only 15% of all cases, a rate that is much lower than rates in Manitoba (29%) (15), Northwestern Ontario (42%) (10), and in children in Utah (8).

Nontypeable H. influenzae has been the most common isolate in virtually all published series among adults. In our study, it accounted for 43% of cases; similar rates were reported in other studies (3,7,15–17). The emerging role of invasive disease because of nontypeable strains is intriguing because this organism has traditionally been considered a relatively noninvasive bacteria predominantly associated with community-acquired pneumonia, chronic obstructive pulmonary disease exacerbations, and otitis media (18). Whether invasive strains of nontypeable H. influenzae have distinct genotypic and phenotypic characteristics compared with noninvasive isolates remains largely unknown. Candidate virulence factors include the adhesin genes hmw and hia and IS1016, an insertion element that may confer Hib-like, encapsulated properties to nontypeable strains. However, to date no single set of virulence determinants has been conclusively associated with invasive nontypeable strains (19–21). Better understanding of the factors that confer invasive capabilities might lead to improved strategies for vaccine development.

Similar to the findings in Spain, Illinois, and Alaska, rates of disease in our study were highest among older patients (3,5,7). The incidence increased in persons >65 years of age, and 29% of infections in this age group were fatal, emphasizing the disproportionate effect. Invasive H. influenzae was highly associated with concurrent illness. Among those for whom clinical data were available, 67% of our patients had an underlying condition, as has been observed in other studies (3,7). However, in those with and without concurrent illness, invasive H. influenzae showed a high overall case-fatality rate (22%). Other studies have reported that invasive H. influenzae is associated with high mortality rates, ranging from 13% to 29% (3,4,6,7). During 2005–2008, the CDC Active Bacterial Core surveillance reported case-fatality rates of 13%–17% for invasive H. influenzae (22). Among adults >65 years of age, the incidence of invasive H. influenzae, the case-fatality rate and the number of attributable deaths exceeds that for invasive meningococcal disease in the most vulnerable age group, those 11–19 years of age (23). However, no vaccine is available for invasive disease caused by encapsulated non-type b and nontypeable H. influenzae. Efforts to prevent invasive H. influenzae, particularly among the elderly, should become a public health priority.

As with all surveillance studies, our study is subject to several limitations. The UDoH relies on passive reporting of H. influenzae from laboratories throughout the state, making underreporting likely. However, a study of invasive H. influenzae in Spain among children <5 years of age demonstrated that passive surveillance had a sensitivity of 88% (24). Comparison of estimated rates from the IH laboratory database and UDoH surveillance data suggests that the sensitivity of reporting among adults was 65%. Changes in reporting behavior and changes to the passive surveillance program in 2005 are potential sources of bias. Several studies have demonstrated the inaccuracy of serotyping compared with molecular diagnostic techniques (25,26). Although serotyping is still an accepted standard, had we performed capsular gene analysis, it might have changed the serotype distribution. Additionally, the small number of identified cases places limitations on analyses of serotype distribution and clinical characteristics. Finally, we had clinical information on concurrent conditions for only 57% of the cohort, and clinical information was not collected in a systematic manner across the state.

These limitations notwithstanding, we found that the incidence of invasive H. influenzae in Utah adults appears to be increasing, and this increase is caused mostly by the rising incidence of nontypeable H. influenzae and Hif. Invasive H. influenzae, including disease caused by nontypeable strains, has a high mortality rate. Persons >65 years of age are most affected by the disease and have the highest death rates. These data have implications for targeted adult H. influenzae vaccine development.