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Table 1.  

Demographic Age-standardized average incidence, 1992–2002 Age-standardized incidence, 2018 Absolute increase in age-standardized incidence Age-standardized incidence risk ratio, 2018 to 1992–2002 baseline (95% CI) Increase in age-standardized incidence, %
Age group, y, not standardized
   0–4 0.03 0.01 −0.03 0.16 (0.02–1.19) −83.52
   5–14 0.02 0.01 −0.01 0.48 (0.15–1.54) −51.61
   15–24 0.07 0.19 0.12 2.80 (2.19–3.57) 179.80
   25–34 0.18 0.75 0.58 4.30 (3.79–4.88) 330.31
   35–44 0.38 1.97 1.59 5.15 (4.74–5.59) 414.89
   45–54 0.66 4.12 3.46 6.28 (5.91–6.69) 528.44
   55–64 1.02 6.52 5.50 6.39 (6.05–6.75) 539.14
   65–74 1.42 7.66 6.24 5.40 (5.11–5.70) 439.63
   75–84 1.57 8.52 6.96 5.44 (5.07–5.84) 444.13
   ≥85 1.49 9.69 8.20 6.50 (5.82–7.27) 550.35
Sex
   M 0.63 3.66 3.04 5.86 (5.67–6.05) 485.55
   F 0.35 1.86 1.50 5.29 (5.06–5.53) 429.22
Race*
   Native American or Alaska Native 0.26 1.27 1.01 4.93 (3.51–6.93) 392.94
   Asian or Pacific Islander 0.14 0.56 0.42 4.03 (3.19–5.10) 303.18
   Black or African American 0.47 5.21 4.74 11.04 (10.39–11.73) 1003.95
   White 0.37 1.99 1.61 5.30 (5.12–5.49) 430.15
Region
   Division
Northeast 0.68 4.82 4.14 7.04 (6.70–7.40) 604.10
   New England 0.61 4.33 3.72 7.10 (6.40–7.87) 610.04
   Middle Atlantic 0.71 5.00 4.30 7.07 (6.69–7.48) 606.98
South 0.33 1.97 1.64 5.97 (5.67–6.29) 497.23
   South Atlantic 0.44 2.29 1.85 5.24 (4.91–5.59) 423.54
   East South Central 0.32 2.05 1.73 6.40 (5.63–7.27) 539.66
   West South Central 0.15 1.36 1.21 9.15 (8.10–10.34) 815.03
Midwest 0.67 4.10 3.43 6.13 (5.85–6.42) 513.06
   East North Central 0.77 5.01 4.24 6.48 (6.16–6.82) 548.02
   West North Central 0.42 2.04 1.62 4.81 (4.29–5.40) 381.38
West 0.29 0.99 0.70 3.39 (3.11–3.68) 238.50
   Mountain 0.43 1.07 0.64 2.47 (2.15–2.83) 146.55
   Pacific 0.23 0.95 0.72 4.13 (3.71–4.59) 312.91
United States 0.48 2.71 2.23 5.67 (5.52–5.83) 467.30

Table. Magnitude of increase in age-standardized incidence of Legionnaires’ disease, cases/100,000 population, from 1992–2002 (average) through 2018, United States

*Ethnicity was not analyzed because data were missing for 30.4% of cases.

CME / ABIM MOC

Rising Incidence of Legionnaires’ Disease and Associated Epidemiologic Patterns, United States, 1992–2018

  • Authors: Albert E. Barskey, MPH; Gordana Derado, PhD; Chris Edens, PhD
  • CME / ABIM MOC Released: 2/17/2022
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 2/17/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for infectious disease specialists, primary care physicians, and other physicians who care for patients at risk for LD.

The goal of this activity is to assess the epidemiology of LD in the US over the past 3 decades.

Upon completion of this activity, participants will:

  1. Analyze trends in the incidence of Legionnaires' disease (LD) according to age
  2. Assess trends in the incidence of LD according to sex
  3. Evaluate trends in the incidence of LD according to race
  4. Distinguish the geographic regions and seasons associated with the highest rates of LD


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Faculty

  • Albert E. Barskey, MPH

    Centers for Disease Control and Prevention
    Atlanta, Georgia

  • Gordana Derado, PhD

    Centers for Disease Control and Prevention
    Atlanta, Georgia

  • Chris Edens, PhD

    Centers for Disease Control and Prevention
    Atlanta, Georgia

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine

    Disclosures

    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor

  • Jill Russell, BA

    Copyeditor 
    Emerging Infectious Diseases

    Disclosures

    Disclosure: Jill Russell, BA, has disclosed no relevant financial relationships.

CME Reviewer

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.


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CME / ABIM MOC

Rising Incidence of Legionnaires’ Disease and Associated Epidemiologic Patterns, United States, 1992–2018: Discussion

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Discussion

Reported incidence of LD in the United States has been rising since 2003, and the increase appears to be accelerating in recent years. Joinpoint analysis confirmed that a change in trend in age-standardized incidence occurred between 1996 and 2002, inclusively; no trend was identified before the change point, and an increasing trend was identified after. Although 1999 was indicated as the single optimal change point, and age-standardized incidence increased slightly every year after 1999 until 2004, the first substantial increase beyond what was likely the baseline range occurred in 2003. However, the rising incidence was not uniform and affected some demographic groups disproportionately. Increases tended to be larger in demographics with higher incidence. This rise was most strikingly associated with increases in racial disparities, geographic focus, and seasonality. We also noted changes in age and sex distributions.

The US population is aging[16–18]; because older age is a risk factor for LD[2] and incidence increased with age, the aging population might contribute to the rising national incidence of LD. In this analysis, age-standardized incidence increased less than crude incidence. However, this difference was minor (12% in 2018), and relative increases in incidence from the baseline years to 2018 for all age groups older than 34 years were at least equal to the national average, suggesting that other factors played larger roles in the rising trend.

Although most LD cases occurred among White persons, Black or African American persons were disproportionately affected. Certain underlying conditions, including diabetes, end-stage renal disease, and some cancers, have been associated with an increased risk for LD[2], and these conditions are more common among Black or African American persons than White persons[19–22]. Social determinants of health also likely contributed to disparities in incidence[23]. Black or African American persons had the lowest median household income relative to other races[24], and areas of poverty were associated with a higher incidence of LD[25,26]. Residence in areas with more vacant housing, more renter-occupied homes, more homes built before 1970, and lower education levels were also identified as risk factors for LD[26]. Certain occupations (transportation, repair, protective services, cleaning services, and construction) were found to carry a higher risk for LD, but the associations with race and socioeconomic status were unclear[25]. The relative increase in LD incidence from baseline years to 2018 was larger among Black or African American persons than any other demographic group, suggesting that the conditions leading to this disparity have been worsening.

Geographically, LD incidence was generally focused around an area extending from Ohio into New York state and Maryland and decreased with distance from this center. Although incidence rose nationwide, areas with higher incidence tended to have larger increases. These findings indicate that factors shared by geographic areas might have contributed to the rise in cases. Several studies found temperature, precipitation, and humidity to be associated with LD cases, although the mechanics are not completely understood[27–31]. Aging infrastructure might also have played a role, because residing in areas with older homes has been identified as a risk factor for LD[26]. Median population age varied by jurisdiction; the Northeast region had the highest median population age, followed by the Midwest, South, and West regions[17]. However, standardizing age across jurisdictions for 2018 did not dramatically alter the jurisdiction-specific incidence from the crude incidence, suggesting that geographic variations in population age did not account for the higher incidence observed in the Middle Atlantic, East North Central, and New England divisions to a large extent.

LD exhibits a summer-through-early-fall seasonality, and this pattern became more pronounced as incidence increased, which could imply that the cyclical factors causing seasonal patterns are becoming more extreme. One likely candidate for a cyclical factor that could cause seasonal patterns in LD cases is weather. From 1990–2020, summer precipitation and the fall mean temperature have been increasing in high-incidence divisions[32]. Our results and previous findings suggest that the peak of the LD season shifted from late summer to mid-summer, particularly in the Northeast and Midwest regions[11]. Wetter summers might partly explain this shift, because precipitation and humidity have been associated with increased cases[27–31]. Similarly, temperatures in the South reach Legionella-promoting temperatures, which also increase cooling tower use, earlier in the year than in the Northeast or Midwest, which might explain why the LD season begins first in the South[33]. Furthermore, hurricane-produced rainfall increased during 1998–2016[34], and hurricanes have been associated with elevated concentrations of Legionella bacteria in cooling towers and surface water[35,36]. Travel is also a cyclical risk factor for LD but does not appear to influence seasonality; seasonal patterns for travel-associated cases were nearly identical to those for non–travel-associated cases during 2015–2016[37]. Furthermore, the percentage of travel-associated cases remained relatively stable over time[37].

LD might occur worldwide because Legionella is a ubiquitous freshwater bacterium[38], but reporting and surveillance vary considerably. Patient demographics and a general rise in incidence were similar in the United States, Europe, Canada, and Australia, but the trajectory of the rising incidence trend was more similar in northern hemisphere locations than Australia (Figure 8)[39–42]. This finding could suggest that factors common to northern regions, such as weather patterns, influenced the increase. In Ontario, Canada, just north of the high-incidence Middle Atlantic and East North Central divisions, LD incidence was generally highest in the southern part of the province, north of Lakes Erie and Ontario[41]. Reasons for the worldwide increase in LD are unclear but might include an aging population, surveillance and reporting improvements, building infrastructure design and maintenance, and weather patterns[39,40].

Enlarge

Figure 8. International crude incidence (cases/100,000 population) trends of Legionnaires’ disease, United States (National Notifiable Diseases Surveillance System), Europe[39], Ontario, Canada[40,41], and Australia[42], 1991–2018.

The first limitation of our study is that, when evaluating rising incidence, separating the effect of improved surveillance from a true increase in infections is difficult. NNDSS is a passive surveillance system, and incomplete case-reporting is a concern with passive systems; however, a comparison with an active reporting system suggested that nearly all diagnosed LD cases were reported[43]. LD might be underdiagnosed; studies estimate that 20,000 cases might occur annually[2,44]. Because of the severe acute respiratory syndrome pandemic during 2002–2003[45], practitioners might have increased the thoroughness of testing community-acquired pneumonia (CAP) patients to confirm an alternative diagnosis, thereby increasing the number of LD tests performed[29]. Although this factor might explain the initial rise in reported LD cases in the United States, it does not explain the continued increase through 2018 or why increases did not occur simultaneously in other areas of the world, particularly Ontario, where severe acute respiratory syndrome cases occurred most outside of Asia[45]. Although the case definition changed twice during our study period, the differences were small and unlikely to have substantially affected diagnosis or reporting. All case definitions included a positive urinary antigen test, isolation of Legionella spp., and a ≥4-fold rise in antibody titer to L. pneumophila serogroup 1 as options for confirming a case[13–15]; most cases were confirmed by 1 of these methods[1,46]. Before 2006, the direct fluorescent antibody test was also included, but its use in diagnosis had been declining since the mid-1990s[46]. At the same time, the urinary antigen test came into widespread use and by 1998 was used in the diagnosis of >70% of reported cases[46]. Therefore, changes in the case definition or available diagnostic tests are unlikely to account for the rising incidence after 2002.

Despite these limitations, our findings indicate several instructive points. Although professional guidelines recommend testing for Legionella in CAP patients associated with certain factors, such as an LD outbreak or recent travel, or in adults with severe CAP[47], clinicians might maintain a higher index of suspicion for LD in other CAP patients under certain circumstances because LD cases are rising nationwide and cannot be diagnosed on clinical features alone. Our results showed LD incidence was highest in older persons (particularly ≥55 years of age) and Black or African American persons, but these demographic groups also tended to have the highest rates of pneumonia-associated hospitalizations[48]. Because LD incidence was highest in the East North Central, Middle Atlantic, and New England divisions, and pneumonia-associated hospitalization incidence was not similarly higher in these divisions[48], the likelihood that a CAP case is LD might be elevated in these locations. Similarly, more LD cases occurred during the summer and early fall, especially in the Northeast and Midwest, but most pneumonia-associated hospitalizations occurred during December–March[48]; therefore, a larger percentage of CAP cases during the summer and early fall might be LD. Others have suggested increasing suspicion for LD in CAP patients during warm, humid, rainy weather[27].

In conclusion, LD incidence has risen steadily nationwide for >15 years, and the increase was associated with wider racial disparities, intensifying geographic focus, and more pronounced seasonality. The geographic focus and seasonality suggest that deeper investigations into the effects of weather may further elucidate the rising incidence of LD. Although WMPs are recommended for buildings with complex water systems and certain devices[3–5], uptake might be slow[49], and additional prevention methods could be useful. Outbreaks can cause substantial illness and deaths[50], but ≈64% of reported LD cases have no known potential exposure and generally lack an identified source[1]. Improved investigations of sporadic cases and their sources may lead to novel prevention strategies and the identification of previously unrecognized outbreaks.