Global Incidence and Mortality of Severe Fungal Disease

Abstract

Background: Current estimates of the incidence of fungal disease are imprecise and were last published in 2017. The number of deaths linked to fungal disease is previously estimated at 1.5 and 2.0 million. Here these estimates are revised.

Methods: Population at risk denominators were used to estimate annual incidence, usually 2019-2021. Extensive literature searches from 2010-2023 were combined with >80 individual published country and global burden papers. Crude and attributable mortality was estimated using a combination of the untreated mortality,  the proportion who are treated, and the survival percentage in treated patients. Awareness, guidelines, accessibility of diagnostics and therapies informed the ratio of treated to untreated cases. Estimates do not account for influenza or Covid-19 outbreaks. Over 250 published papers from >120 countries contributed data.

Findings: Annually, over 2,113,000 people suffer from invasive aspergillosis in the context of COPD, intensive care, lung cancer and haematological malignancy, with an estimated 1,801,000 deaths (85.2%). The annual incidence of chronic pulmonary aspergillosis is estimated at 2,484,000 with an annual mortality 460,000 (18.5%). About 1,433,000 suffer from Candida bloodstream infection or invasive candidiasis with 911,000 deaths (63.6%). Pneumocystis pneumonia affects 505,000 with 214,000 deaths (42.4%). Cryptococcal meningitis affects 194,000 with 147,000 deaths (75.8%). Other major life-threatening fungal infections affect ~300,000 and lead to 161,000 deaths (53.7%). Fungal asthma is common affecting ~11.5 million and may contribute to 46,000 asthma deaths annually (~10% of the total asthma deaths). These updated estimates suggest ~3.8 million annual deaths from fungal infection of which ~2.6 million (67.6%, range 35-90%) were directly attributable.

Interpretation: These new estimates are necessarily crude with large variability in the underlying risk populations, major regional differences, significant differences in the proportions affected in different studies, uncertainty in the mortality rate of undiagnosed and untreated patients and in the ratio of diagnosed to undiagnosed patients for a given disease.

Funding: No external funding.

Declaration of Interest: David Denning reports no direct conflicts of interest. He and his family have held Founder shares since 1998 in F2G Ltd, a University of Manchester spin-out antifungal discovery company, and share options in TFF Pharma. He acts or has recently acted as a consultant to Pulmatrix, Pulmocide, Biosergen, TFF Pharmaceuticals, Pfizer, Omega, Novacyt, Rostra Therapeutics, MucPharm, Mundipharma, Lifemine and Cipla. He chairs a Data Review Committee for Pulmocide and as Phase 1 Medical Monitor for Biosergen. In the last 3 years, he has been paid for talks on behalf of BioRad, Basilea and Pfizer. He is a longstanding member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines group and recently joined the One World Guideline for Aspergillosis.

Keywords: Aspergillus, Candida Cryptococcus, Histoplasma, Pneumocystis Talaromyces, Mucormycosis, Antifungal, Diagnosis