Aspergillosis-Attributable Mortality in the United States: Analysis of Death Certificate Data

Background The nationwide attributable mortality of aspergillosis in the era of mold-active triazoles is poorly understood. Prior studies have used death certificates to evaluate mortality rates associated with invasive fungal diseases, however, they used older data and provided limited insights into death due to aspergillosis alone. Methods We analyzed data from the US National Vital Statistics System for 2018-2024. Aspergillosis-attributable mortality was identified using an International Classification of Diseases-10th-Revision diagnosis code of B44.x listed anywhere on a death certificate. We present age-adjusted mortality rates (AAMRs)/1,000,000 persons with 95% confidence intervals (CIs) for aspergillosis deaths and stratified by demographics. Risk ratios (RRs) were used to compare AAMRs across strata and the proportion of key comorbidities included on aspergillosis versus non-aspergillosis certificates. Results There were 7063 aspergillosis-attributable deaths identified (AAMR=2.43, 2.37-2.49), with 22.0% listing aspergillosis as the primary cause. An invasive aspergillosis (IA) disease code was most often listed (n=4880 certificates); specifically, ‘other pulmonary aspergillosis’ (B44.1, n=4292). Unspecified aspergillosis was listed on 2139 death certificates. Aspergillosis deaths increased in later years of analysis (AAMR range: 2.50-3.01) versus 2018-2020 (AAMR=2.01). Nearly 60% of aspergillosis deaths occurred in those ≥65-years-old, and the AAMR was higher in males (RR=1.64, 1.50-1.80). Neither race nor ethnicity were associated with differences in AAMR. AAMRs varied across states. Conclusions Among patients with a death certificate with aspergillosis, primary attributable mortality was 22.0%. Our results may be useful as experts seek to better understand the true epidemiology of aspergillosis, develop efforts to raise disease awareness, and reduce aspergillosis-related mortality.