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Increase in Reported Coccidioidomycosis — United States, 1998–2011

Coccidioidomycosis, also known as valley fever, is an infection caused by inhalation of Coccidioides spp. spores. This soil-dwelling fungus is endemic to arid regions of Mexico, Central and South America, and the southwestern United States (1). Symptomatic patients typically experience a self-limited influenza-like illness, but some develop severe or chronic pulmonary disease, and less than 1% of patients experience disseminated disease (1). Coccidioidomycosis can be costly and debilitating, with nearly 75% of patients missing work or school because of their illness, and more than 40% requiring hospitalization (2). Previous publications have reported state-specific increases in coccidioidomycosis in Arizona and California during 1998–2001 and 2000–2007, respectively (3,4). To characterize long-term national trends, CDC analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) for the period 1998–2011. This report describes the results of that analysis, which indicated that the incidence of reported coccidioidomycosis increased substantially during this period, from 5.3 per 100,000 population in the endemic area (Arizona, California, Nevada, New Mexico, and Utah) in 1998 to 42.6 per 100,000 in 2011. Health-care providers should be aware of this increasingly common infection when treating persons with influenza-like illness or pneumonia who live in or have traveled to endemic areas.

In collaboration with the Council of State and Territorial Epidemiologists (CSTE), CDC compiles data on selected diseases through NNDSS. Data are reported to CDC from various state and territorial surveillance systems and reporting mechanisms. Coccidioidomycosis has been nationally notifiable since 1995; however, it was not nationally notifiable in 2010. Although the CSTE case definition includes both laboratory and clinical criteria, Arizona uses a laboratory-only case definition because of its large number of cases and the high predictive value of a positive laboratory result (2); since 2008, the laboratory component of the CSTE definition has included cases with a single positive serologic test. California uses the CSTE case definition, requiring both laboratory and clinical evidence of infection, but some counties with large numbers of cases use a laboratory-only definition.

State and regional annual incidence rates were calculated by dividing the number of cases by U.S. Census Bureau population estimates for each year. Crude, sex-specific, age-specific, and age-adjusted incidence rates (aIR) were calculated for Arizona, California, and other endemic states where coccidioidomycosis is reportable (Nevada, New Mexico, and Utah, combined). Rates were age adjusted using the 2000 U.S. standard population. Negative binomial regression was performed to assess statistical significance of incidence trends during 1998–2011. This model adjusts for changes in population size and age and sex distribution over time.

During 1998–2011, a total of 111,717 coccidioidomycosis cases were reported to CDC from 28 states and the District of Columbia: 66% from Arizona, 31% from California, 1% from other endemic states, and <1% from nonendemic states. In Arizona, California, Nevada, New Mexico, and Utah combined, the number of cases increased from 2,265 in 1998 (aIR: 5.3 per 100,000 population) to 8,806 in 2006 (18.0 per 100,000); a decrease occurred in 2007 and 2008 before an increase in 2009 (12,868 cases; 25.3 per 100,000), which continued into 2010 and 2011 (42.6 per 100,000) (Table 1).

Incidence in endemic states increased among all age groups during 1998–2011 (Figure). During this period, incidence typically was highest among the 40–59 year age group in California but was consistently highest among persons aged ≥60 years in Arizona and other endemic states. Incidence during 2011 was 381.1 per 100,000 among persons aged 60–79 years and 385.2 per 100,000 among persons aged ≥80 years in Arizona (Table 2).

During 1999–2008, most (56%) Arizona cases occurred among males, but beginning in 2009, a higher proportion (55%) of cases occurred among females. Incidence in 2011 in Arizona was substantially higher among females (286.9 per 100,000) than males (215.7 per 100,000). In contrast, only 35% of California cases occurred among females during 1998–2011, and 2011 incidence among California males (20.5 per 100,000) was more than double that among females (9.7 per 100,000).

The increase in the number of Arizona cases, from 1,474 in 1998 to 16,467 in 2011, was statistically significant by negative binomial regression (aIR: 30.5 per 100,000 in 1998; 247.7 per 100,000 in 2011, p<0.001). Adjusting for changes in population demographics, this corresponds to an increase in coccidioidomycosis incidence of approximately 16% each year during the study period. The number of California cases increased from 719 in 1998 (aIR: 2.1 per 100,000) to 5,697 in 2011 (aIR: 14.9 per 100,000) (average annual increase of 13%, p<0.001). The number of cases reported in Nevada, New Mexico, and Utah combined increased from 72 in 1998 (aIR: 1.4 per 100,000) to 237 in 2011 (aIR: 3.1 per 100,000) (p<0.001). Cases reported in nonendemic states increased from six in 1998 to 240 in 2011.

Reported by

Clarisse A. Tsang, MPH, Arizona Dept of Health Svcs. Farzaneh Tabnak, PhD, Duc J. Vugia, MD, California Dept of Public Health. Kaitlin Benedict, MPH, Tom Chiller, MD, Benjamin J. Park, MD, Div of Foodborne, Waterborne, and Environmental Diseases, CDC. Corresponding contributor: Kaitlin Benedict, kbenedict@cdc.gov, 404-639-0387.

Editorial Note

This report describes statistically significant increases in the incidence rate of reported coccidioidomycosis in endemic states during 1998–2011 after adjusting for changes in population size and in age and sex distribution. Although the number of cases decreased in Arizona during 2007–2008 and in California during 2007–2009, incidence dramatically increased in 2010 and 2011. In 2011, coccidioidomycosis was the second most commonly reported nationally notifiable condition in Arizona and the fourth most commonly reported in California (5).

The reasons for the increases described in this report are unclear. Coccidioides exists in the soil and is sensitive to environmental changes; factors such as drought, rainfall, and temperature might have resulted in increased spore dispersal, and disruption of soil by human activity, such as construction, also might be a contributing factor.

Changes in surveillance methodology might have resulted in artifactual increases. California transitioned to a laboratory-based reporting system during 2010, which facilitated reporting and might account for the increase in reported cases in 2011. However, some highly endemic counties, such as Kern County, already had been using laboratory-based systems, so this cannot fully explain the recent increase. The observed increase in Arizona might be partially attributable to a 2009 change by a major commercial laboratory to conform its reporting practices to the 2008 CSTE case definition, whereby positive enzyme immunoassay (EIA) results were reported as cases without confirmation by immunodiffusion. One commercially available EIA test (Meridian Bioscience) commonly used to diagnose coccidioidomycosis has been described to have false-positive results in some instances (6), but the contribution of this phenomenon, if any, to the overall increase in cases is unknown.

Improved awareness of coccidioidomycosis might have resulted in increased diagnostic testing (and thus reporting) in endemic and nonendemic states. Coccidioides has been found to be the etiologic agent in an estimated 15%–29% of community-acquired pneumonias in highly endemic areas (7). However, a 2006 study demonstrated that only a small proportion (2%–13%) of patients with compatible illness in an endemic area were tested for coccidioidomycosis (7), suggesting that the disease is greatly underreported. Further study is needed to understand if testing practices have changed. Despite the increase in reported cases, overall U.S. coccidioidomycosis mortality rates have remained fairly stable at approximately 0.6 per 1 million person-years during 1990–2008 (8).

The findings in this report are subject to at least four limitations. First, NNDSS data might underrepresent the actual burden of disease because coccidioidomycosis is not reportable in every state, even in known endemic areas such as Texas, and because state reporting of cases to CDC is voluntary. In particular, the number of cases reported in 2010 might underestimate the actual number of infections because coccidioidomycosis was not notifiable in 2010 (but became notifiable again in 2011). Second, minor discrepancies between the findings in this report and those presented in MMWR's annual Summary of Notifiable Diseases reports likely exist because the summary does not include cases from states where the disease was not reportable. Third, minor discrepancies might exist between this report and state-specific reports because of delays in case reporting. Finally, because nearly 70% of cases were missing race/ethnicity data, incidence rates by race and ethnicity were not calculated. This is an important consideration because high rates among Asians and blacks have been documented previously, and black race has been shown to be an independent risk factor for disseminated coccidioidomycosis (9).

Further investigation is needed to determine how much of the observed increase in coccidioidomycosis incidence is artifactual. Nevertheless, health-care providers should be alert for coccidioidomycosis among patients of all ages who live in or have traveled to endemic areas. Persons in endemic areas should consider trying to reduce exposure to dusty air, which might contain Coccidioides spp. spores. However, because there are currently no proven preventive measures for coccidioidomycosis, additional research into strategies that reduce the incidence or morbidity of this infection is warranted. Specifically, the role of antifungal treatment for primary pulmonary disease remains controversial and deserves further exploration (10), although treatment is recommended in certain patient groups, particularly those at high risk for severe disease (1). Because the symptoms of coccidioidomycosis mimic those of other community-acquired respiratory illnesses, patients often experience delays in testing and diagnosis and receive unnecessary antibiotics; however, patients who know about coccidioidomycosis are more likely to request testing and receive a diagnosis sooner than those who are not familiar with the disease (2). Therefore, promoting increased community and health-care provider awareness of this infection continues to be an important role for public health officials.

Acknowledgments

National Notifiable Diseases Surveillance System. Div of Notifiable Disease Surveillance, Public Health Surveillance Program Office, Office of Surveillance, Epidemiology, and Laboratory Services, CDC.

References

  1. Galgiani JN, Ampel NM, Blair JE. Coccidioidomycosis. Clin Infect Dis 2005;14:1217–23.
  2. Tsang CA, Anderson SM, Imholte SB, et al. Enhanced surveillance of coccidioidomycosis, Arizona, USA, 2007–2008. Emerg Infect Dis 2010;16:1738–44.
  3. CDC. Increase in coccidioidomycosis—Arizona. MMWR 2003;52:109–12.
  4. CDC. Increase in coccidioidomycosis—California. MMWR 2009;58:105–9.
  5. CDC. Final 2011 reports of nationally notifiable infectious diseases. MMWR 2012;61:624–37.
  6. Kuberski T, Herrig J, Pappagianis D. False-positive IgM serology in coccidioidomycosis. J Clin Microbiol 2010;48:2047–9.
  7. Chang DC, Anderson S, Wannemuehler K, et al. Testing for coccidioidomycosis among patients with community-acquired pneumonia. Emerg Infect Dis 2008;14:1053–9.
  8. Huang JY, Bristow B, Shafir S, et al. Coccidioidomycosis-associated deaths, United States, 1990–2008. Emerg Infect Dis 2012;18:1723–8.
  9. Rosenstein NE, Emery KW, Werner SB, et al. Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995–1996. Clin Infect Dis 2001;32:708–15.
  10. Ampel NM, Giblin A, Mourani JP, Galgiani JN. Factors and outcomes associated with the decision to treat primary pulmonary coccidioidomycosis. Clin Infect Dis 2009;48:172–8.

What is already known on this topic?

Coccidioidomycosis is an infection that results from inhalation of Coccidioides spp. fungal spores. It is endemic in the southwestern United States, with the highest number of cases occurring in Arizona and California, and constitutes a substantial public health burden in these areas, particularly among older persons.

What is added by this report?

Reported coccidioidomycosis cases have increased dramatically in recent years. The age-adjusted incidence was 5.3 cases per 100,000 population in the endemic area in 1998 and 42.6 per 100,000 in 2011. Among persons aged 60–79 years in the endemic area, incidence was 69.1 cases per 100,000 in 2011.

What are the implications for public health practice?

The number of reported cases of coccidioidomycosis is increasing. Health-care providers should be alert for this infection among persons with influenza-like illnesses who live in or have traveled to endemic areas. Further research on strategies to reduce the morbidity of coccidioidomycosis is needed.


TABLE 1. Number and age-adjusted incidence per 100,000 population of coccidioidomycosis cases, by region — Arizona, California, Nevada, New Mexico, and Utah, 1998–2011

Year

Arizona

California

Nevada, New Mexico, and Utah

Total endemic area*

No.

Incidence

No.

Incidence

No.

Incidence

No.

Incidence

1998

1,474

30.5

719

2.1

72

1.4

2,265

5.3

1999

1,812

37.6

939

2.8

55

0.9

2,806

6.6

2000

1,917

36.6

840

2.5

67

1.1

2,824

6.4

2001

2,301

43.1

1,538

4.4

63

1.0

3,902

8.6

2002

3,133

57.2

1,727

4.9

63

1.0

4,923

10.7

2003

2,695

47.8

2,091

5.9

55

0.9

4,841

10.4

2004

3,667

62.9

2,641

7.4

110

1.5

6,418

13.5

2005

3,516

58.3

2,885

7.8

108

1.7

6,509

13.4

2006

5,535

88.6

3,131

8.6

140

2.1

8,806

18.0

2007

4,832

75.0

2,991

8.1

163

2.4

7,986

16.0

2008

4,768

72.5

2,597

7.0

99

1.4

7,464

14.8

2009

10,233

154.4

2,488

6.7

147

2.1

12,868

25.3

2010

11,883

182.0

4,622

12.2

159

2.1

16,664

32.2

2011

16,467

247.7

5,697

14.9

237

3.1

22,401

42.6

* Coccidioidomycosis is endemic but not reportable in Texas.


FIGURE. Coccidioidomycosis incidence per 100,000 population, by age group — Arizona, California, Nevada, New Mexico, and Utah, 1998–2011

The figure shows Coccidioidomycosis incidence per 100,000, by age group, in Arizona, California, Nevada, New Mexico, and Utah during 1998-2011. Incidence in coccidioidomycosis-endemic states increased among all age groups during 1998-2011. During this period, incidence typically was highest among the 40-59 year age group in California but was consistently highest among persons aged ≥60 years in Arizona and other coccidioidomycosis-endemic states.

Abbreviations: CSTE = Council of State and Territorial Epidemiologists; AZ = Arizona; CA = California.

Alternate Text: The figure above shows Coccidioidomycosis incidence per 100,000, by age group, in Arizona, California, Nevada, New Mexico, and Utah during 1998-2011. Incidence in coccidioidomycosis-endemic states increased among all age groups during 1998-2011. During this period, incidence typically was highest among the 40-59 year age group in California but was consistently highest among persons aged ≥60 years in Arizona and other coccidioidomycosis-endemic states.


TABLE 2. Number and incidence per 100,000 population of coccidioidomycosis cases, by region, age group, and sex — Arizona, California, Nevada, New Mexico, and Utah, 2011

Area and age group (yrs)

Male

Female

Total*

No.

Incidence

No.

Incidence

No.

Incidence

Arizona

<5

38

16.5

25

11.3

63

14.0

5–19

621

89.4

796

120.3

1,428

105.3

20–39

1,671

187.1

2,707

319.4

4,422

254.1

40–59

2,239

276.4

3,223

386.5

5,509

335.1

60–79

1,919

382.4

2,078

372.8

4,037

381.1

≥80

424

445.4

461

334.8

897

385.2

All ages

6,954

215.7

9,349

286.9

16,467

254.0

California

<5

35

2.7

22

1.8

57

2.2

5–19

340

8.5

263

6.9

605

7.7

20–39

1,329

24.0

561

10.6

1,897

17.6

40–59

1,513

30.0

583

11.4

2,098

20.6

60–79

509

21.4

337

12.4

848

16.7

≥80

88

18.5

75

9.8

163

13.1

All ages

3,839

20.5

1,844

9.7

5,697

15.1

Nevada, New Mexico, and Utah

<5

0

0.0

0

0.0

0

0.0

5–19

8

0.9

5

0.6

13

0.8

20–39

15

1.4

17

1.7

32

1.5

40–59

49

5.2

29

3.0

77

4.1

60–79

62

12.2

38

7.2

100

9.6

≥80

10

11.6

4

3.2

14

6.6

All ages

143

3.8

93

2.5

237

3.1

Total endemic area

<5

73

4.0

47

2.7

120

3.3

5–19

969

17.4

1,064

20.0

2,046

18.8

20–39

3,015

40.1

3,286

45.8

6,352

43.2

40–59

3,801

55.8

3,834

55.5

7,684

56.0

60–79

2,491

73.4

2,455

90.2

4,988

69.1

≥80

522

79.4

540

52.3

1,074

63.6

All ages

10,398

40.3

11,288

43.4

22,401

43.2

* Categories might not sum to totals because of missing age and sex data.

Coccidioidomycosis is endemic but not reportable in Texas.



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