Invasive fungal infections

Invasive aspergillosis (IA)

Aspergillosis is caused by Aspergillus spp, a group of pathogenic moulds found in the environment.^1,2 Many people inhale Aspergillus spores without experiencing any symptoms, but infection is more likely in those with weakened immune systems.¹

Pathogenesis

Aspergillosis is a term used to describe different types of infections, which include chronic pulmonary aspergillosis (in patients with pre-existing lung injury), allergic bronchopulmonary aspergillosis (in patients with asthma and cystic fibrosis) and invasive pulmonary aspergillosis (in patients who are immunocompromised).^1,3,4

IA is typically caused by colonisation of the lungs by Aspergillus spp., resulting in invasion of lung tissue by hyphae and subsequent angioinvasion; the infection can then disseminate to other organs, including the central nervous system.^3,4

Epidemiology

The global incidence of IA is estimated to be 300,000 cases per year, although this is likely an underestimate due to the difficulties surrounding diagnosis.⁵ Due to the unspecific nature of symptoms, IA is commonly misdiagnosed in the intensive care unit (ICU).^6,7

IA represents a significant contributor to morbidity and mortality in the haemato-oncology setting, the ICU setting and in patients who have undergone transplantation. The case fatality rate is estimated to be close to 90% in high-risk groups, such as bone marrow transplant recipients, and approximately 30% if appropriately managed.^2,6,8,9 Factors associated with poor prognosis in patients undergoing transplant include neutropenia and renal or hepatic insufficiency.⁸

Invasive pulmonary aspergillosis is an emerging co-infection in patients with influenza (influenza-associated pulmonary aspergillosis) and patients with coronavirus disease 2019 (COVID-19-associated pulmonary aspergillosis) who are admitted to the ICU.¹⁰ The viral infection and treatments for the viral infection (e.g., corticosteroids) contribute to this risk.¹¹

Risk factors

Known risk factors for IA include:^3,4,6,8,12

• Haematological and oncological malignancies
• Prolonged neutropenia
• Use of immunosuppressant drugs, such as corticosteroids
• Chronic obstructive pulmonary disease
• Acquired immune deficiency syndrome
• Liver failure
• Chronic granulomatous disease
• Organ transplant recipients
• Respiratory viral infection, such as influenza or COVID-19

Pathogenic species

• A. fumigatus is the most common Aspergillus species implicated in IA infection, and represents a major infectious cause of death¹³
• Several other Aspergillus species have been implicated in IA, including A. flavus, A. niger, A. terreus, A. versicolor, A. calidoustus and A. nidulans¹³

References

1. Latgé JP and Chamilos G. Clin Microbiol Rev. 2019;33:e00140–18.
2. van de Peppel RJ. Managing invasive aspergillosis: impact on health and personalized prevention or treatment strategies (Doctoral dissertation, Leiden University). 2021.
3. WHO fungal priority pathogens list to guide research, development and public health action. Geneva: World Health Organization. Available at: https://www.who.int/publications/i/item/9789240060241. Accessed July 2023.
4. Kosmidis C and Denning DW. Thorax. 2015;70:270–277.
5. Bongomin F et al. J Fungi (Basel). 2017;3:57.
6. Townsend L and Martin-Loeches I. Diagnostics (Basel). 2022;12:2712.
7. Winters B et al. BMJ Qual Saf. 2012;21:894–902.
8. Baddley JW et al. Clin Infect Dis. 2010;50:1559–1567.
9. Lin SJ et al. Clin Infect Dis. 2001;32:358–366.
10. Verweij P et al. Intensive Care Med. 2020;46:1524–1535.
11. Hoenigl M et al. Nat Microbiol. 2022;7:1127–1140.
12. Schauwvlieghe AF et al. Lancet Respir Med. 2018;6:782–792.
13. Lamoth F. Front Microbiol. 2016;7:683.