Methods

Data Source and Collection

CDC uses the National Notifiable Diseases Surveillance System (NNDSS) to track coccidioidomycosis and histoplasmosis from states where the diseases are reportable by mandate and from those where cases are reported voluntarily. Reportable fungal diseases are designated by the state or jurisdiction and require health care professionals and laboratories to notify public health departments of cases. Nationally notifiable diseases such as coccidioidomycosis involve states or jurisdictions voluntarily submitting case data to CDC through NNDSS. Coccidioidomycosis surveillance data were submitted by 26 states (Alabama, Arizona, Arkansas, California, Delaware, Indiana, Kansas, Louisiana, Maryland, Michigan, Minnesota, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Mexico, North Dakota, Ohio, Oregon, Rhode Island, South Dakota, Utah, Washington, Wisconsin, and Wyoming) and the District of Columbia, where it is reportable; in Washington, coccidioidomycosis is reportable as a rare disease of public health significance. All states and jurisdictions where coccidioidomycosis is reportable routinely submit data to NNDSS. Because of the COVID-19 pandemic, the 2019 coccidioidomycosis NNDSS data for California were incomplete; therefore, California submitted state surveillance data directly to CDC's Mycotic Diseases Branch. Histoplasmosis and blastomycosis are not nationally notifiable, and data for these diseases are not submitted to NNDSS by all states where they are reportable. Histoplasmosis information included cases in NNDSS or data directly submitted to CDC from 13 state health departments (Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Nebraska, Pennsylvania, Rhode Island, and Wisconsin); in Rhode Island, histoplasmosis is reportable as a rare or unusual condition. Only Delaware, Illinois, Kentucky, Louisiana, Michigan, Minnesota, Pennsylvania, Rhode Island, and Wisconsin submit data to NNDSS. Blastomycosis surveillance data were directly submitted to CDC from five state health departments (Arkansas, Louisiana, Michigan, Minnesota, and Wisconsin). NNDSS included case-level data, whereas the direct submissions to CDC contained aggregate data. Certain state and local health departments collected clinical and exposure information during their investigations and patient interviews; however, those types of data are not captured in NNDSS for coccidioidomycosis, histoplasmosis, or blastomycosis. States that submitted histoplasmosis and blastomycosis data directly to CDC also provided information on hospitalizations and deaths.

Surveillance Case Definitions

The Council of State and Territorial Epidemiologists (CSTE) established national case definitions for coccidioidomycosis in 2011, histoplasmosis in 2017, and blastomycosis in 2019.^[32–34] The 2011 CSTE coccidioidomycosis definition includes both laboratory and clinical criteria; cases can be classified as confirmed.^[32] Confirmed cases meet the clinical criteria and are laboratory confirmed. The laboratory criteria include culture, histopathologic, and molecular evidence of Coccidioides spp. or a positive serologic test for Coccidioides antibodies. Clinical criteria include symptoms resembling influenza or pneumonia-like illnesses, or the infection can be asymptomatic. In 2019, California and Arizona case data were based on laboratory-only reporting.

The 2017 CSTE histoplasmosis definition includes both laboratory and clinical criteria; cases can be classified as confirmed or probable.^[33] Confirmed cases are clinically compatible with histoplasmosis and meet confirmatory laboratory criteria. Probable cases are 1) clinically compatible and meet nonconfirmatory laboratory criteria, 2) meet confirmatory laboratory criteria but not clinical criteria, or 3) clinically compatible and do not meet laboratory criteria but are epidemiologically linked to a confirmed case. Clinical criteria include symptoms indicative of histoplasmosis, abnormal chest imaging findings, or evidence of disseminated disease. Confirmatory laboratory criteria include culture, histopathology, molecular detection, detection of H band by immunodiffusion antibody test or detection of M band after a previous lack of M band, or a greater than fourfold rise in antibody titer. Nonconfirmatory laboratory criteria include cytopathology or a single positive antibody or antigen enzyme immunoassay (EIA) test.

The 2019 CSTE blastomycosis definition includes both laboratory and clinical criteria; cases can be classified as confirmed or probable.^[34] Confirmed cases are clinically compatible with blastomycosis and meet confirmatory laboratory criteria. Probable cases are 1) clinically compatible and meet presumptive laboratory criteria, 2) clinically compatible and do not meet laboratory criteria but are epidemiologically linked to a confirmed case, or 3) laboratory confirmed but no clinical information is available. Clinical compatibility requires relevant symptoms, abnormal chest imaging findings, or evidence of disseminated disease. Confirmatory laboratory criteria include identification of Blastomyces by culture, histopathology, cytopathology, or molecular detection. Presumptive laboratory criteria include detection of Blastomyces antigen at or above the minimum level of quantification in serum, urine, or other body fluid by EIA test or detection in serum of antibodies against Blastomyces by immunodiffusion. Reporting states might have used different case classification criteria during 2019 before adopting the national case definition in 2020.

Analysis

The analysis included confirmed coccidioidomycosis cases and confirmed or probable histoplasmosis and blastomycosis cases from all states that reported at least one of these fungal diseases in 2019. Analyzed data included case counts, case classification, sex, age, ethnicity and race, and the earliest recorded event month and type (symptom onset, diagnosis, laboratory test, or date reported to the county or state health department). States with coccidioidomycosis cases were classified based on incidence according to endemicity in certain states: high endemicity (Arizona and California), low endemicity (Nevada, New Mexico, Utah, and Washington), or not known to be endemic. These analytic groupings were chosen because Arizona and California report most cases. Coccidioides is also known to be present in Nevada, New Mexico, Utah, and Washington, although these states report fewer cases than Arizona and California, and cases reported from other states are typically travel associated.^[35] Analyses of histoplasmosis and blastomycosis cases were stratified by individual state. For each disease, state-specific incidence rates per 100,000 population by sex, age, and race and ethnicity categories were calculated using 2019 U.S. Census Bureau state-specific denominators for each category.^[36] The "other" race and ethnicity category was calculated using the two or more race variable from U.S. Census Bureau data. For seasonality, spring included March, April, and May; summer included June, July, and August; autumn included September, October, and November; and winter included December, January, and February. Descriptive analyses were completed in RStudio (version 4.0.3; R Foundation). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.*

*See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. ^§241(d); 5 U.S.C. ^§552a; and 44 U.S.C. ^§3501 et seq.