Economic Burden of Fungal Diseases in the United States

Abstract

We conservatively estimated the US economic burden of fungal diseases as $11.5 billion in 2019: direct medical costs ($7.5 billion), productivity loss due to absenteeism ($870 million), and premature deaths ($3.2 billion). An alternative “value of statistical life” approach yielded >$48 billion. These are likely underestimates given underdiagnosis and underreporting.

We conservatively estimated the U.S. economic burden of fungal diseases as $11.5 billion in 2019: direct medical costs ($7.5 billion), productivity loss due to absenteeism ($870 million), and premature deaths ($3.2 billion). These are likely underestimates given underdiagnosis and underreporting.

Fungal diseases cause a wide range of illnesses, including skin and mucosal infections, pneumonia, and life-threatening disseminated infections. Signs and symptoms of fungal diseases are often similar to those of bacterial or viral infections, which can lead to delays in diagnosis and treatment and, consequently, poor patient outcomes.

Because fungal diseases are likely widely underdiagnosed, the total burden is difficult to quantify. We previously calculated direct medical costs associated with fungal diseases in the United States; however, indirect costs have not been examined [1]. More comprehensive estimates of the economic burden of fungal diseases are needed to inform resource prioritization for their prevention, diagnosis, and treatment.

METHODS

We estimated the cost of fungal diseases in 2019, which comprises direct medical costs and indirect costs due to productivity loss from absenteeism and premature deaths. We used published estimates of hospitalizations, outpatient visits, and direct medical costs for 11 fungal diseases: aspergillosis, blastomycosis, invasive candidiasis, noninvasive candidiasis, coccidioidomycosis, cryptococcosis, dermatophytosis, histoplasmosis, Pneumocystis pneumonia, mucormycosis, and other and unspecified mycoses [1]. In brief, these estimates were based on health insurance claims data from the IBM MarketScan Research Databases, national hospital discharge data from the Healthcare Cost and Utilization Project (HCUP), and outpatient visit data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey [1]. Direct medical costs, originally reported in 2017 dollars, were adjusted to 2019 dollars for this analysis using the Personal Health Care Expenditure index [2].

To calculate productivity loss, we used a human capital approach, a common method for cost-of-illness calculations that considers a person’s production potential. Productivity loss due to absenteeism was calculated as the product of missed workdays (outpatient visits and nonfatal hospitalizations) and the average wage rate, among working-age patients. Missed workdays from nonfatal hospitalizations was based on the disease-specific average length of stay (Table 1). We added 5 days for recovery outside the hospital for all diseases except for noninvasive candidiasis and dermatophytosis. For coccidioidomycosis, histoplasmosis, and blastomycosis, we used a conservative assumption of 2 missed workdays per outpatient visit, based on expert opinion and observations that many patients with these diseases miss substantial time away from work aside from time spent visiting a healthcare provider [3]. For all other diseases, we assumed 0.25 missed workdays (2 hours) per outpatient visit [4]. We used an average hourly wage of $25.72 for 2019, doubled to account for overhead and benefits [5].

Table 1.

Disease-Specific Inputs Used to Estimate Economic Burden of Fungal Diseases, United States, 2019

Disease	Hospitalizationsa	Outpatient Visitsa	Average Workdays Lost per Hospitalizationb	Proportion of Nonfatal Hospitalizations Among Working-Age Patientsc	Deathsd
Aspergillosis	14 820	e	20.3	52%	723
Blastomycosis	950	e	13.2	68%	60
Candida infection
Invasive candidiasis	12 770	e	28.4	50%	655
Noninvasive candidiasis	13 990	3 639 037	5.9	42%	537
Coccidioidomycosis	6670	e	13.4	67%	192
Cryptococcosis	4755	e	19.7	70%	334
Dermatophytosis	690	4 981 444	3.7	65%	36
Histoplasmosis	4630	79 993	13.4	61%	133
Pneumocystis pneumonia	10 590	e	16.6	78%	436
Mucormycosis	1140	e	25.6	61%	134
Other and unspecified mycoses	7355	222 523	22.1	57%	1645

Source: Benedict et al [1].

Source: length of stay from the 2014 National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality, plus 5 additional days for recovery outside the hospital for all diseases except for noninvasive candidiasis and dermatophytosis.

Source: 2014 National Inpatient Sample, HCUP, Agency for Healthcare Research and Quality. We used the same proportions of working-age patients for outpatient visits.

Source: 2019 Multiple-Cause-of-Death data, available at https://wonder.cdc.gov/.

Estimate suppressed according to National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey protocols.

Productivity loss due to premature deaths was calculated using single-year age estimates of future productivity (both market and nonmarket) with a 3% discount rate and a 0.5% productivity growth rate [6]. Estimates were adjusted to 2019 dollars using the Bureau of Labor Statistics’ Employment Cost Index [7]. We used Multiple Cause of Death data to identify deaths in 2019 with a fungal disease listed as an underlying or contributing cause of death (based on International Classification of Diseases, 10th Edition [ICD-10] codes) for single-year-ages and assumed all deaths occurred during hospitalization.

Patient Consent Statement

This study did not include factors necessitating patient consent.

RESULTS

The estimated economic burden of fungal diseases was $11.5 billion for 2019 (Table 2). Direct medical costs ($7.5 billion) accounted for approximately two thirds of the total costs. Productivity loss was estimated to be $870 million for absenteeism (~2.1 million missed workdays) and $3.2 billion for premature deaths.

Table 2.

Economic Burden of Fungal Diseases, United States, 2019

Disease	Direct Medical Costs	Productivity Losses From Workdays Lost Due to Hospitalizations	Productivity Losses From Workdays Lost Due to Outpatient Visits	Productivity Losses From Premature Deaths	Total Economic Burden
Aspergillosis	$1 291 497 039	$64 749 568	$1 629 791	$419 411 905	$1 777 288 304
Blastomycosis	$24 075 459	$3 503 953	$1 875 481	$44 289 490	$73 744 383
Candida Infection
Invasive candidiasis	$1 240 388 451	$75 219 548	$501 819	$446 944 883	$1 763 054 702
Noninvasive candidiasis	$2 129 492 530	$14 198 320	$156 492 565	$272 990 358	$2 573 173 773
Coccidioidomycosis	$204 254 578	$24 496 036	$15 098 644	$141 237 843	$385 087 101
Cryptococcosis	$265 266 472	$26 868 318	$820 762	$241 638 975	$534 594 527
Dermatophytosis	$845 434 279	$677 644	$330 556 668	$8 423 048	$1 185 091 639
Histoplasmosis	$222 446 966	$15 650 824	$10 089 587	$84 602 342	$332 789 720
Pneumocystis pneumonia	$489 284 857	$56 065 629	$461 170	$298 512 981	$844 324 636
Mucormycosis	$129 012 825	$7 374 017	$13 581	$123 704 121	$260 104 544
Other and unspecified mycoses	$897 365 285	$37 927 041	$12 980 425	$1 117 224 732	$2 065 497 482
Total	$7 463 346 840	$326 730 897	$530 520 495	$3 198 980 677	$11 519 578 908

Approximately one third of the total economic burden was from noninvasive candidiasis ($2.6 billion) and dermatophytosis ($1.2 billion) combined, another 30% was from invasive candidiasis ($1.8 billion) and aspergillosis ($1.8 billion) combined, and “other and unspecified mycoses” ($2.1 billion) comprised approximately 20% of the total economic burden.

DISCUSSION

Fungal diseases are associated with a substantial economic burden, including both direct and indirect costs. We used a conservative method to estimate indirect costs, which only includes productivity loss due to missed workdays and premature deaths. These estimates do not include intangible costs such as pain, missed personal or educational activities, and indirect effects to families. An alternative approach, which would include such intangible costs, involves willingness to pay for a reduction in illness and mortality [8]. Using a population average value per statistical life of $10 million [9], the 4885 fungal disease-related deaths from 2019 are estimated to result in an economic burden of >$48 billion.

Noninvasive candidiasis and dermatophytosis, which are common in the general population, represented approximately one third of total economic burden, suggesting they are of public health importance despite their typically lower severity compared with other fungal diseases. It is notable that noninvasive candidiasis was reported on many death certificates, which suggests that it can be associated with substantial mortality, although it may also be a marker for other critical illnesses. Direct medical costs associated with noninvasive candidiasis were also substantial, likely reflecting, in part, the tremendous burden of vulvovaginal candidiasis [10]. Invasive candidiasis and aspergillosis, which were recorded on the highest number of death certificates, comprised an approximately equivalent proportion of costs as the noninvasive mycoses, although their share would be far higher using an average value per statistical life approach. These diseases warrant continued focus on prevention and treatment interventions.

Previous estimates of the economic burden of coccidioidomycosis, specifically in Arizona ($736 million in 2019) [11] and California ($700 million in 2017) [12], are substantially higher than our conservative estimate of $385 million nationwide. These state-specific studies include assumptions and direct costs unaccounted for in our analysis, for example, costs of medical care before establishing a coccidioidomycosis diagnosis and long-term costs of follow-up care and medication. In other words, these studies estimate the lifetime burden of coccidioidomycosis, whereas our direct medical costs primarily capture acute care related to hospitalizations and outpatient visits within 1 year.

Our analysis is subject to several limitations, including those described in our original estimates of direct medical costs [1]. Namely, potential coding misclassification is inherent in fungal disease-related hospitalizations and outpatient visit data. This limitation also applies to death certificate data; the large number of deaths with “unspecified mycosis” recorded as an underlying cause indicates that better diagnosis and coding practices are needed. In general, fungal diseases appear to be widely underdetected as a cause of death [13, 14], so our estimates of productivity loss due to premature deaths are underestimated due to low detection and underreporting. Therefore, our estimates are likely to be more conservative than burden estimates for other infectious diseases such as influenza and foodborne illness, which extrapolate numbers of deaths based on in-hospital mortality or case fatality ratios, rather than relying directly on death certificate data [15, 16]. As an indication of the extent to which death certificates likely undercount fungal deaths, crude comparisons of hospitalizations (via HCUP data) and deaths (via death certificates) yield hospitalization-fatality ratios of 5%–12% for aspergillosis, candidiasis, and mucormycosis, whereas data from clinical trials and public health surveillance show case-fatality ratios of 30%–60%, suggesting that deaths may be 5 to 6 times higher than reported. However, HCUP data and death certificates are not directly comparable, primarily because patients may be hospitalized multiple times with a fungal disease within 1 year. Death counts 5 times higher than reported would yield an economic burden of $24.3 billion.

Our estimates also do not include costs associated with unnecessary testing and inappropriate treatment before a fungal disease diagnosis is established. Such costs could be substantial because fungal diseases are frequently misdiagnosed. In addition, many patients with fungal diseases have severe underlying conditions, such as cancer, solid organ or stem cell transplantation, or advanced human immunodeficiency virus. We were unable to account for the influence of underlying conditions in this analysis, but fungal diseases are well known to result in prolonged hospitalizations and excess costs and mortality among at-risk patients [17–20]. Finally, our analysis did not account for over-the-counter (OTC) antifungal treatment, given the lack of comprehensive sales data [21]. The OTC antifungals are frequently used for vaginal candidiasis and dermatophyte infections; one source estimated that sales for OTC “feminine itch & yeast treatment” and “jock itch” medication were $300 million and $57 million, respectively, in 2019 [22]. These costs are not inconsequential but are relatively small compared with our overall estimates. Studies focused on specific fungal pathogens can produce improved estimates incorporating costs associated with misdiagnosis, underlying conditions, and antifungal treatment.

CONCLUSIONS

In conclusion, the economic burden of fungal diseases is substantial, owing to their considerable morbidity and mortality. Increased attention to fungal disease prevention, diagnosis, and treatment is needed.