We used the 2021 Healthcare Cost and Utilization Project (HCUP) National Inpatient Survey (NIS) (https://hcup-us.ahrq.gov/nisoverview.jsp) to estimate total numbers of fungal disease-associated hospitalizations in the United States. The NIS is the largest publicly available all-payer US hospitalization database, representing a ~20% stratified sample of all discharges from community hospitals and covering >97% of the population. Discharge weights allow calculation of national estimates; the weighted NIS estimates ~35 million total hospitalizations annually.

We used the 2022 Merative™ MarketScan® Commercial, Medicare, and Multi-State Medicaid Databases (https://www.merative.com/documents/merative-marketscan-research-databases) to obtain numbers of fungal disease-associated outpatient visits and mean costs per outpatient visit and per hospitalization. The MarketScan® databases are among the largest US health insurance claims-based databases and are widely used for public health and health services research. The 2022 Commercial and Medicare Databases represent a convenience sample of ~20 million employees, dependents, and retirees covered by employer-sponsored insurance including Medicare Supplemental and Medicare Advantage plans. The databases enable calculations of weights to project the convenience sample to the entire US population with employer-sponsored insurance; the weights are based on Census division, age group, sex, and policy holder status from the US Census Bureau’s American Community Survey. The Multi-State Medicaid Database is structured similarly to the Commercial/Medicare Database and represents a convenience sample of ~8 million patients from several geographically dispersed states.

We used 2023 Final Multiple Cause of Death data from the National Vital Statistics System (NVSS) using the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) platform (https://wonder.cdc.gov/mcd.html) to identify fungal disease-associated deaths. These mortality data for all US residents are based on death certificates.

For each data source, we used the most recent year of finalized data available and International Classification of Diseases, Tenth Revision, Clinical Modification codes to identify fungal diseases (Table S1).

We estimated total national direct medical costs of fungal disease-associated hospitalizations and outpatient visits from a healthcare payer perspective. These costs represent the sum of payments to insurers and patient out-of-pocket costs. All costs incurred at a hospitalization or outpatient visit were included, even if fungal disease was not the main diagnosis. For each setting (hospital and outpatient), we calculated disease-specific costs by insurance type: Medicare, Medicaid, private insurance, and “other,” which includes self-pay and other government programs. We used the privately-insured mean cost per hospitalization and outpatient visit for “other” insurance types.¹

To calculate total national hospitalization costs, we multiplied national hospitalization numbers from HCUP by mean hospitalization costs. We used numbers of outpatient visits among the entire US population with employer-sponsored insurance from the weighted MarketScan® estimates combined with proportions of the US population with each insurance type,⁶ to extrapolate to total outpatient visits among persons without employer-sponsored insurance. To calculate total national outpatient visit costs, we multiplied national outpatient visits by mean outpatient costs.

We calculated indirect costs due to absenteeism and premature deaths using a human capital approach.² Productivity loss from absenteeism was calculated for patients <65 years old by multiplying missed workdays from a) nonfatal hospitalizations (Table S1) and b) outpatient visits by the 2023 mean hourly wage of $31.48, doubled to account for overhead and benefits.⁷ We used a conservative assumption of 2 missed workdays per outpatient visit for coccidioidomycosis, histoplasmosis, and blastomycosis and 0.25 missed workdays per visit for all other diseases.^2,8 To calculate productivity loss from premature deaths, we multiplied numbers of deaths by future market and nonmarket productivity (3% discount rate and a 0.5% productivity growth rate) for the average age at fungal disease-associated death.⁹ We assumed all deaths occurred during hospitalization. All costs were adjusted to 2024 dollars using the medical Consumer Price Index.¹⁰