The landscape of invasive fungal infections is changing

This website is developed and fully funded by Gilead Sciences Europe Limited

3D image of Aspergillus

The landscape of invasive fungal infections is changing1-10

An increasing variety of rare, resistant, and post-viral fungal infections have been observed globally.1-14 Explore the spectrum of invasive fungal infections (IFIs) and how it has continued to evolve across the world.

SUMMARY OF THE GLOBAL BURDEN OF IFIs16
Bar chart showing summary of global burden of IFIs; invasive candidiasis has the highest incidence

IFIs ARE AN EMERGING GLOBAL CONCERN15

Invasive candidiasis and invasive aspergillosis account for the majority of IFIs worldwide, with ~700,000 and >300,000 cases each year, respectively.16 Mucormycosis is a rare IFI with a frequency of >10,000 cases each year, although cases have been increasing in recent years.16,17 Additional IFIs, including cryptococcosis and histoplasmosis, are highly prevalent in regions where untreated HIV and AIDS are common, including Sub-Saharan Africa, South America and South-East Asia.18
DISTRIBUTION OF CANDIDA ALBICANS ISOLATES BY GEOGRAPHIC REGION: SENTRY 2000–2016*19
Bar chart showing distribution of Candida albicans isolates by geographic region

CANDIDA ALBICANS REMAINS THE MOST COMMON CAUSE OF IFIs GLOBALLY21,22

Up to 82% of fungal infections worldwide were caused by Candida species in 2013, according to global surveillance conducted as part of the SENTRY Program.**20 C. albicans was consistently the predominant species, and remains responsible for the majority of candidiasis and candidaemia cases worldwide, accounting for almost 50% of Candida infections.†16,19 Recent estimates provide a range of 70-90% for global fungal infections caused by Candida across different settings.21,22

Furthermore, antifungal resistance is rising amongst Candida species, a cause for great concern with respect to managing this common IFI.23

RARE AND RESISTANT CANDIDA SPECIES ARE ON THE RISE23

Although Candida albicans remains the most commonly reported pathogen, non-albicans infections have risen and account for ~50% of all invasive candidiasis cases.21 Increasing cases of C. glabrata, C. tropicalis, C. parapsilosis and C. krusei have been reported over the past several years. Furthermore, the concerning increase of multi-drug resistant C. auris poses a serious global health threat due to its ability to survive in hospital environments and cause lengthy outbreaks, propensity to acquire resistance mechanisms and potential to be misidentified by current diagnostic systems.23

INCREASING NON-ALBICANS CANDIDAEMIA HAS BEEN OBSERVED GLOBALLY23

Map showing increasing incidence of non-albicans candidaemia globally

Invasive candidiasis is most commonly associated with critical care settings22

Icon representing incidence

Invasive candidiasis (IC) affects ~700,000 people globally every year16

Icon of fungal pathogens

Candida species account for 70-90% of IFIs21

Icon showing exclamation mark

IC is associated with a mortality rate of 30-60%, despite treatment16,22

ASPERGILLUS SPECIES CAN CAUSE DIFFICULT-TO-TREAT INFECTIONS24

Aspergillus infections are globally distributed and A. fumigatus is the leading cause of aspergillosis.16,24,25

Over recent years, A. flavus and A. terreus have been frequently reported in specific centres but remain uncommon in most geographic regions:26

  • A. flavus is predominantly found in Asia, the Middle East, and Africa, which may be due to its improved survival in hot or arid climatic conditions compared with other Aspergillus species27
  • The increasing prevalence of A. terreus in certain regions may be affected by a combination of meteorological factors, pH values, vegetation, and topographical positions28

Increasing cases of C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei have been reported over the past several years.16 The rise in Aspergillus infections is a particular concern due to azole-resistant strains, which are in danger of becoming a global health threat.29

The incidence of invasive aspergillosis is increasing1,2,30

Icon representing incidence

Invasive aspergillosis (IA) affects >300,000 people annually8

Icon showing people

~10 million people at risk of developing IA each year16,31

Icon showing exclamation mark

IA mortality rates can be as high as 70%16,31

The steady rise in aspergillosis cases may also be due to the increasing number of patients with weakened immune systems, i.e. patients with cancer or those who have undergone solid organ transplantation.24,33 Invasive pulmonary aspergillosis has also been observed as a secondary infection in patients with COVID-19 and influenza.14,34
Microscopic image of fungal pathogens in a Petri dish

MUCORALES SPECIES ARE INCREASINGLY CAUSING INFECTIONS WITH A HIGH MORTALITY RATE12

A steep rise in the number of mucormycosis cases has recently been reported in developing countries, such as India, particularly rhino-orbital mucormycosis in patients with COVID-19 or uncontrolled diabetes or those treated with corticosteroids.35,36 Mucormycosis has also emerged as the second most common breakthrough infection following prophylactic antifungal treatment in patients undergoing haematopoietic stem cell transplantation (HSCT) and in patients with haematological malignancies.37

Mucormycosis infections are increasing, particularly in endemic countries35,36

Icon representing incidence

Mucormycosis affects 0.005 to 1.7 per million population globally36

Icon showing map outline of India

Estimated prevalence was 140 cases per million population in India in 2021 – 80 times higher than in other parts of the world37

Icon showing exclamation mark

Mortality rates for mucormycosis range between 46-96%38-40

Aspergillus niger mold under the microscope

The most common species of Mucorales are the Rhizopus species, although others belonging to the order, such as Mucor, Rhizomucor, Lichtheimia, Mycocladus, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces and Syncephalastrum, have been reported.24

The classical risk factors for mucormycosis are uncontrolled diabetes and injuries or wounds in the skin; however, immunosuppression and granulocytopenia have become the most common predisposing factors in many tertiary hospitals over recent years.24

CRYPTOCOCCUS SPECIES ARE A MAJOR CAUSE OF HIV-RELATED DEATHS WORLDWIDE41

Improved access to antiretroviral therapy has transformed the prognosis of people living with HIV.42 However, cryptococcal meningitis remains one of the leading causes of death in HIV patients in sub-Saharan Africa, where 75% of global deaths from cryptococcal meningitis occur every year.41,43 Cryptococcus neoformans and Cryptococcus gattii are the most common causative species of cryptococcal meningitis.44

Cryptococcal meningitis is associated with high mortality rates and detriment to quality of life43,45

Icon representing incidence

~250,000 patients are affected by cryptococcal meningitis (CM) globally per year44

Icon of fungal pathogens

CM contributes to 10-20% of all HIV-related deaths worldwide41

Icon showing exclamation mark

Mortality rate of 100% if CM infection remains untreated44

Some species, such as Cryptococcus tetragattii (known to only occur in Africa and India) can be dormant or latent for 20-30 years after exposure in patients with HIV.41 Fatal cryptococcal meningitis usually occurs in patients at advanced stages of HIV.41

FUSARIUM SPECIES CONTRIBUTE TO MORTALITY IN HSCT PATIENTS46

In Brazil, Fusarium species have become a leading cause of invasive fungal disease in haematological patients and may be the second most common nosocomial fungal pathogen after Aspergillus in some tertiary hospitals.24 Fusarium solani is the most common and virulent species, comprising approximately 40-60% of infections globally.47 Additionally, treatment poses challenges as a higher level of antifungal resistance has been observed in Fusarium vs. Aspergillus species.24

The incidence of fusariosis is increasing globally47

Icon representing incidence

6 cases of fusariosis per 1,000 HSCTs in Brazil46

Icon showing exclamation mark

Mortality rate of over 75% if fusariosis infection remains untreated24

Treatment poses challenges as a higher level of antifungal resistance has been observed in Fusarium vs Aspergillus species.24 The main risk factor for invasive fusariosis is neutropenia, predominantly in patients with acute myeloid leukaemia and HSCT recipients.24
Microscopic image of fungal pathogens

Know your enemy

Stay one step ahead of IFIs by understanding their strengths, weaknesses, and target patients.

Discover more

Footnotes

*The SENTRY global antifungal surveillance programme was established to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-onset infections. Clinical isolates were collected from 39 countries across the globe under the following objectives: bloodstream, skin and skin structure, respiratory, urinary tract, intra-abdominal and IFIs, as well as pathogens from patients hospitalised with pneumonia.19

**A total of 1846 clinical isolates were collected as part of a global surveillance during 2013. Among those, 1514 (82.0%) were Candida species, 114 (6.2%) were noncandidal yeasts including cryptococcus neoformans (84, 4.5%), 196 (10.6%) were Aspergillus species and 22 (1.2%) were other moulds. Isolates were geographically distributed among Europe (41.0%), the Asia-Pacific (24.5%), North America (23.5%) and Latin America (11.0%).20

†Among the 20,788 Candida isolates submitted for testing as part of the SENTRY Program from 1997-2016, 46.9% were C. albicans, 18.7% were C. glabrata, 15.9% were C. parapsilosis, 9.3% were C. tropicalis, 2.8% were C. krusei and 6.5% were miscellaneous Candida species. The rank order of the 5 most common species varied slightly over time, although C. albicans was the predominant species every year.19

References

  1. Taccone FS et al. Critical Care. 2015;9:7.
  2. Verweij PE et al. Intensive Care Med. 2020;46:1524-1535.
  3. Cornillet A et al. Clin Infect Dis. 2006;43(5):577-584.
  4. Bassetti M et al. Crit Care. 2019;23(1):219.
  5. Evert K et al. Virchows Arch. 2021;1-12.
  6. Loughlin L et al. Am J Respir Crit Care Med. 2020;202(8):1125-1132.
  7. Hoenigl, M et al. (2021). The emergence of COVID-19 associated mucormycosis: Analysis of cases from 18 countries. Available at: https://www.researchgate.net/publication/351558444 [Last accessed: November 2022].
  8. Wiederhold NP. Infect Drug Resist. 2017;29;10:249-259.
  9. Bassetti M et al. Crit Care. 2014;18(4):458.
  10. Meersseman W et al. Am J Respir Crit Care Med. 2004;170(6):621-625.
  11. Peman J et al. Rev Iberoam Micol. 2020;37(2):41-46.
  12. Moorthy A et al. J Maxillofac Oral Surg. 2021;20(3):418-425.
  13. Song G et al. Mycopathologica. 2020;185(4):599-606.
  14. Dewi IMW et al. Curr Opin Microbiol. 2021;62:21-7.
  15. Kainz K et al. Microb Cell. 2020;7(6):143-145.
  16. Bongomin F et al. J Fungi (Basel). 2017;3(4):57.
  17. Skiada A et al. Med Mycol 2018; 56:S93-S101.
  18. Limper AH et al. Lancet Infect Dis. 2017;17:e334-e343.
  19. Pfaller MA et al. Open Forum Infect Dis. 2019;6(Suppl 1):S79-S94.
  20. Castanheira M et al. Diagnos Micro Infect Dis. 2016;85:200-204.
  21. Zhang Z et al. BMJ Open. 2020;10:e036452.
  22. Logan C et al. Intensive Care Med. 2020;46(11):2001-2014.
  23. Pappas PG et al. Nat Rev Dis Primers. 2018;11;4:18026.
  24. Lass-Flörl C and Cuenca-Estrella M. J Antimicrob Chemother. 2017;46(1):62-68.
  25. Warris A and Verweij PE. Med Mycol. 2005;43:S59-S65.
  26. Azie N et al. Diagnos Micro Infect Dis. 2012;73(4):293-300.
  27. Rudramurthy SM et al. J Fungi (Basel). 2019;5(3):55.
  28. Dietl AM et al. Microorganisms. 2021;9(3):539.
  29. Verweij PE et al. Drug Resist Updat. 2015;21-22:30-40.
  30. Mercier T et al. Crit Care. 2020;24:642.
  31. Sun KS et al. PLoS One. 2017;12(10):e0186422.
  32. Tomiyama T et al. Surg Case Rep. 2021;12;7(1):118.
  33. Al-Bader N and Sheppard DC. Virulence. 2016;7(8):950-966.
  34. Dimopoulos G et al. J Inten Med 2021; DOI: doi.org/10.1016/j.jointm.2021.07.001.
  35. Chakrabarti A and Singh R. Mycoses. 2014;57(Suppl 3):85-90.
  36. Singh AK et al. Diabetes Metab Syndr. 2021;15(4):102146.
  37. Skiada A et al. J Fungi (Basel). 2020;6(4):265.
  38. Prakash H et al. Med Mycol. 2019;57(4):395-402.
  39. Jeong W et al. Clin Microbiol Infect. 2015;25(1):26-34.
  40. Roden MM et al. Clin Infect Dis. 2005;41(5):634-53.
  41. Okurut S et al. Mycoses. 2020;63:840-853.
  42. Srichatrapimuk S and Sungkanuparph S. AIDS Res Ther. 2016;13:42.
  43. Goralska K et al. Infection. 2018;46:443-459.
  44. Iyer KR et al. Nat Rev Microbiol. 2021;8:1-13.
  45. Pasquier E et al. Clin Infect Dis. 2017;66(7):1122-1132.
  46. Moretti ML et al. PLoS One. 2018;13(4):e0196426.
  47. Batista BG et al. Rev Soc Bras Med Trop. 2020;53:e20200013.

Date of preparation: November 2022. Job code IHQ-AMB-0793.