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The landscape of invasive fungal infections is changing

3D image of Aspergillus

The landscape of invasive fungal infections is changing1

An increasing variety of rare, resistant, and post-viral fungal infections have been observed globally.2-7 Explore the spectrum of invasive fungal infections (IFIs) and how it has continued to evolve across the world.

SUMMARY OF THE GLOBAL BURDEN OF IFIs8
Bar chart showing summary of global burden of IFIs; invasive candidiasis has the highest incidence

IFIs ARE AN EMERGING GLOBAL CONCERN1

Invasive candidiasis and invasive aspergillosis account for the majority of IFIs worldwide, with ~750,000 and >300,000 cases each year, respectively.8 Mucormycosis is a rare IFI with a frequency of >10,000 cases each year, although cases have been increasing in recent years.8,9 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.10
DISTRIBUTION OF CANDIDA ALBICANS ISOLATES BY GEOGRAPHIC REGION: SENTRY 2006-2016.*11
Bar chart showing distribution of Candida albicans isolates by geographic region

CANDIDA ALBICANS REMAINS AS THE MOST COMMON CAUSE OF IFIs GLOBALLY8,12

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.**12 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.8,11

Furthermore, antifungal resistance is rising amongst Candida species, a cause for great concern with respect to managing this common IFI.13

RARE AND RESISTANT CANDIDA SPECIES ARE ON THE RISE13

Although Candida albicans remains as the most commonly reported pathogen, non-albicans infections have risen and account for ~50% of all invasive candidiasis cases.14 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.13

INCREASING NON-ALBICANS CANDIDAEMIA HAS BEEN OBSERVED GLOBALLY13

Map showing increasing incidence of non-albicans candidaemia globally

Invasive candidiasis (IC) is most commonly associated with critical care settings15

ASPERGILLUS SPECIES CAN CAUSE DIFFICULT-TO-TREAT INFECTIONS16

Aspergillus infections are globally distributed and A. fumigatus is the leading cause of aspergillosis.8,16,17

Over recent years, A. flavus and A. terreus have been frequently reported in specific centres but remain uncommon in most geographic regions:18

  • 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 to other Aspergillus species19
  • The increasing prevalence of A. terreus in certain regions may be affected by a combination of meteorological factors, pH values, vegetation, and topographical positions20

The extensive use of antifungal prophylaxis has changed the epidemiology of IFIs by reducing the number of infections caused by Candida species.21 The rise in Aspergillus infections is a particular concern due to azole-resistant strains, which are in danger of becoming a global health threat.22

The incidence of invasive aspergillosis (IA) is increasing3,23,24

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 transplants.16,26 Invasive pulmonary aspergillosis has also been observed as a secondary infection in patients with COVID-19 and influenza.27,28
Microscopic image of fungal pathogens in a Petri dish

MUCORALES SPECIES ARE INCREASINGLY CAUSING INFECTIONS WITH A HIGH MORTALITY RATE6

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.29,30 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.31

Mucormycosis infections are increasing, particularly in endemic countries29,30

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.16

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.16

CRYPTOCOCCUS SPECIES ARE A MAJOR CAUSE OF HIV-RELATED DEATHS WORLDWIDE33

Improved access to antiretroviral therapy has transformed the prognosis of people living with HIV.34 However, cryptococcal meningitis is one of the leading causes of death in HIV patients in low-income countries.31,32 Cryptococcus neoformans and Cryptococcus gattii are the most common causative species of cryptococcal meningitis.35

Cryptococcal meningitis (CM) is associated with high mortality rates and detriment to quality of life36,37

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.33 Fatal cryptococcal meningitis usually occurs in patients with advanced stages of HIV.33

FUSARIUM SPECIES CONTRIBUTE TO MORTALITY IN HAEMATOPOIETIC STEM-CELL TRANSPLANTATION PATIENTS38

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.16 Fusarium solani is the most common and virulent species, comprising approximately 40-60% of infections globally.39 Additionally, treatment poses challenges as a higher level of antifungal resistance has been observed in Fusarium vs. Aspergillus species.16

The incidence of fusariosis is increasing globally39

Treatment poses challenges as a higher level of antifungal resistance has been observed in Fusarium vs. Aspergillus species.16 The main risk factor for invasive fusariosis is neutropenia, predominantly in patients with acute myeloid leukaemia and haematopoietic stem cell transplant recipients.16
Microscopic image of fungal pathogens

Know your enemy

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

Footnotes

*The SENTRY global antifungal surveillance program 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 invasive fungal infections, as well as pathogens from patients hospitalised with pneumonia.11

**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%).12

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.11

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Date of preparation: April 2022. Job code IHQ-AMB-0423.