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Improve your knowledge of invasive fungal diseases (IFDs)

Stay informed on the World Health Organization’s (WHO) priority pathogens, the burden of these infections and which patients are at risk.

3D rendering of Cryptococcus neoformans

Fungi are a diverse, widespread and unique group of organisms.1

Fungi were first identified approximately 1 billion years ago and can be found in a huge range of habitats.1,2 While approximately 144,000 species have been classified to date, currently only 200 species are known to associate with humans – whether as commensals or as pathogens.1,3

There are four key features that set fungi apart from other organisms:1

Red icon of a petri dish

Saprophytic or parasitic

Obtain energy from decaying or living matter.

Red icon of filled and unfilled hexagons linked together

Structurally simple

Basic structural unit, either hyphae or single cells.

Red icon of an oblong cell with many protrusions

Heterotrophic

Secrete enzymes for external digestion; nutrients are then absorbed through the cell wall.

Red icon of a DNA double helix

Eukaryotic

Rigid cell wall and DNA is contained within the nucleus.

Pathogenic fungi can have different morphologies: Yeasts and moulds. Some can switch between these morphologies, which are known as dimorphic fungi.4,5

The fungal cell wall is a key defining feature of fungal cells;4,8,9 it consists of outer mannoproteins, followed by a β-glucan layer, a chitin layer and an inner cell membrane layer.8 The unique nature of the fungal cell wall makes it an ideal drug target.9

3D rendering of Candida albicans

Yeasts, e.g. Candida:4–6

  • Grow as single cells
  • Usually reproduce by budding (asexual reproduction)
  • Usually form smooth, flat, conically shaped colonies
3D rendering of Aspergillus

Moulds, e.g. Aspergillus:4,5,7

  • Multicellular, organised into hyphae, with/without cross walls or branching
  • Asexual or sexual reproduction
  • Colonies usually appear fuzzy
Coccidioides

Dimorphic fungi, e.g. Coccidioides4,5

  • Grow in two distinct morphological forms, correlating with the saprophytic and parasitic modes of growth
  • They grow as moulds in vitro (20–25°C), and as either yeast cells or spherules in vivo (37°C)

Fungal infections are sometimes classified as either opportunistic or primary:10

Red icon of a round cell with many protrusions

Opportunistic

Infections that mainly occur in immunocompromised hosts

Red icon of a round cell with many protrusions

Primary

Infections that can develop in immunocompetent hosts, and usually result from inhalation of fungal spores

Infections caused by fungi are called mycoses; they range from superficial to life-threatening invasive infections.10

Superficial fungal infections are localised to specific areas of the body. They typically involve the skin, nails, mucosa or vagina (causing candidal vaginitis).10

Invasive fungal infections typically occur in immunocompromised hosts and can involve the dissemination of fungi throughout the body via the bloodstream, resulting in sepsis and metastatic fungal abscesses.10–12 

Invasive infections are often more difficult to treat than local infections and can also affect organs, such as the lungs, bone, liver, spleen or central nervous system.10

Aspergillus spp. under a light microscope at 40× magnification after staining

IFDs are a major global health concern.13,14

Serious fungal diseases affect more than 150 million people worldwide, and are responsible for over 1.6 million deaths per year.13

 

IFDs are an important cause of morbidity and mortality, particularly in patients with altered immune function, and overall cases have been rising.14

Coronavirus disease 2019 (COVID-19) has been associated with an increase in the incidence of comorbid IFDs such as aspergillosis, mucormycosis and candidemia, often with harmful consequences.14

Precise estimates of global prevalence and incidence of each fungal infection remain unknown; data are insufficient in some countries, especially those in low-to-middle income countries.13

Knowledge on the global incidence of fungal diseases has been impaired by a lack of regular national surveillance systems, no obligatory reporting of cases of fungal diseases, poor clinician investigation outside of specialised units, poor diagnostic test performance and few well-designed published studies.13

Global burden and annual incidence of fungal diseases
A graph showing the global burden and annual incidence of 25 fungal diseases

Figure adapted from Bongomin F et al. J Fungi (Basel) 2017.

ABPA, allergic bronchopulmonary aspergillosis; AIDS, acquired immunodeficiency syndrome;

PJP, Pneumocystis pneumonia.

Aspergillus, Candida, Cryptococcus and Pneumocystis account for over 90% of reported fungal-related deaths.15

Global mortality rate

Microscopic image of Aspergillus fumigatus by LPCB stain

Aspergillus fumigatus

30–95%

3D rendering of Candida yeast

Candida albicans

46–75%

Positive blood culture of Cryptococcus neoformans (Gram stain)

Cryptococcus neoformans

20–70%

3D illustration of Pneumocystis jirovecii

Pneumocystis jirovecii

20–80%

WHO priority pathogen list

Figure reproduced from WHO fungal priority pathogens list to guide research, development and public health action. Available at https://www.who.int/publications/i/item/9789240060241.

In 2022, the WHO published the first list of fungal priority pathogens.14

These were based on 10 assessment criteria, which include (listed in no particular order) antifungal resistance, fatality rate, annual incidence, inpatient care and access to diagnostics.14

A list of pathogens was developed, ranked in order of priority from critical to medium. An overall combined ranking was based on a discrete choice experiment global survey for research and development priorities and best–worst scaling for public health importance.14

Some of the pathogens are confined to certain geographical areas or specific populations and thus may not be considered a priority on a global scale; however, they must be considered in the local context.14

At-risk patient populations are drivers of IFDs.13,14

IFDs remain a major cause of morbidity and mortality, largely due to the increase in patients living with conditions that affect immune function.13,14

Patients at high risk of IFDs include those:13,14
  • With underlying health problems, such as chronic lung disease or prior tuberculosis
  • With conditions that result in a weakened immune system, such as HIV, cancer or diabetes mellitus
  • Who are critically ill in an intensive care unit
  • Undergoing invasive medical procedures
  • Receiving broad-spectrum antibiotics
  • Who are receiving chemotherapy
  • Who are receiving immunosuppressant drugs
  • Who are recipients of solid organ or bone marrow transplantation
New groups at risk of IFDs are constantly being identified, including patients with:14,16
  • Chronic obstructive pulmonary disease and other structural lung diseases
  • Liver or kidney disease
  • Severe viral respiratory tract infections, such as influenza and COVID-19
  • Prior non-tuberculous mycobacterial infections

IFDs can be subdivided by their morphology into yeasts and moulds. Fungi that can switch between the two are known as dimorphic.4,5

Select a type from the list to view details

Mould infections

Invasive aspergillosis (IA)

Rare mould infections

Lomentosporiosis

 

Scedosporiosis

Dimorphic fungal infections

Coccidiomycosis

Histoplasmosis

Paracoccidioidomycosis

Yeast infections

Cryptococcosis

Invasive candidiasis (IC)

Yeast-like infections

Pneumocystis pneumonia (PJP)

Photo of a person in a laboratory harvesting colonies from a petri dish

Discover more about diagnostics

Comprehensive information on the different methodologies used to diagnose IFDs, and guidance on how to interpret the results of diagnostic tests.

References

  1. Encyclopaedia Britannica. Fungus. Available at: https://www.britannica.com/science/fungus. Accessed July 2023.
  2. Loron CC et al. Nature. 2019;570:232–235.
  3. Fisher MC et al. MBio. 2020;11:e00449–20.
  4. McGinnis MR and Tyring SK. Introduction to Mycology. In: Baron S et al (eds). Medical Microbiology (fourth edition). Galveston, TX: University of Texas Medical Branch at Galveston, 1996.
  5. Microbe Online. Difference between yeast and mold. Available at: https://microbeonline.com/difference-between-yeast-and-mold/. Accessed July 2023.
  6. Vulin C et al. Biophys J. 2014;106:2214–2221.
  7. Cole GT. Basic Biology of Fungi. In: Baron S et al (eds). Medical Microbiology (fourth edition). Galveston, TX: University of Texas Medical Branch at Galveston, 1996.
  8. Gow NAR et al. Microbiol Spectr. 2017;5.
  9. Hasim S, Coleman JJ. Future Med Chem. 2019;11:869–883.
  10. Walsh TJ and Dixon DM. Spectrum of Mycoses. In: Baron S et al (eds). Medical Microbiology (fourth edition). Galveston, TX: University of Texas Medical Branch at Galveston, 1996.
  11. Delaloye J and Calandra T. Virulence. 2014;5:161–169.
  12. Antachopoulos C, Walsh TJ and Roilides E. Eur J Pediatr. 2007;166:1099–1117.
  13. Bongomin F et al. J Fungi (Basel). 2017;3:57.
  14. 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.
  15. Brown GD et al. Sci Transl Med. 2012;4:165rv13.
  16. Sarden N, Yipp BG. Trends Immunol. 2023;44:305–318.

SciA-AFN-2300020 | July 2023