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Fungi & invasive fungal infections

The Gilead Anti-Infectives Forum is a promotional website intended for healthcare professionals in the UK and Ireland, and has been designed, built, and funded by Gilead Sciences Ltd.

Jump to pathogen for more information:

Aspergillus Candida Mucormycetes Cryptococcus

The fungal kingdom includes as many as 6 million species, 600 of which are associated with humans, either as commensal species or as pathogens that can lead to invasive fungal infections (IFIs).1 IFIs are a leading cause of mortality in intensive care units (ICUs),2 haematology3,4 and HIV settings.5-7 With resistance to antifungal treatment on the rise,8,9 you can fight back against the threat by understanding the different fungal pathogens, what invasive fungal diseases they cause, and how they can be treated.

Aspergillus

Aspergillus is a type of ubiquitous saprophytic fungus that can cause invasive infection (aspergillosis) in those who are immunocompromised or have respiratory disease10,11
Most cases of invasive aspergillosis are caused by A. fumigatus, but non-fumigatus Aspergillus species are becoming more common12
The microscopic spores (conidia) present in Aspergillus species are found in the air, soil, dust, decaying vegetation and many other settings; it has been estimated that in excess of 100 A. fumigatus conidia are inhaled by an average adult every day11,13
In most individuals, inhaled conidia will be cleared by the alveolar macrophages, without affecting health. However, Immunocompromised patients are extremely susceptible to local invasion of respiratory tissue by deposited conidia, resulting in invasive growth of hyphae13
Aspergillus is a type of ubiquitous saprophytic fungus that can cause invasive infection (aspergillosis) in those who are immunocompromised or have respiratory disease10,11
Most cases of invasive aspergillosis are caused by A. fumigatus, but non-fumigatus Aspergillus species are becoming more common12
The microscopic spores (conidia) present in Aspergillus species are found in the air, soil, dust, decaying vegetation and many other settings; it has been estimated that in excess of 100 A. fumigatus conidia are inhaled by an average adult every day11,13
In most individuals, inhaled conidia will be cleared by the alveolar macrophages, without affecting health. However, Immunocompromised patients are extremely susceptible to local invasion of respiratory tissue by deposited conidia, resulting in invasive growth of hyphae13

Common and uncommon sites of infection

Common sites of infection

Uncommon sites of infection

NB this list is non-exhaustive

Aspergillus spp. infections in immunocompromised hosts range from pulmonary aspergillosis (the most common site of infection), tracheobronchitis, primary cutaneous aspergillosis (especially in neonates and children), rhinosinusitis, cerebral aspergillosis, to disseminated aspergillosis.13,14 Other unusual sites have also been recorded, including epiglottis and larynx, meninges, endocardium, and renal parenchyma, as well as bone and liver.14

Aspergillus species can cause difficult-to-treat infections15,16

Invasive aspergillosis (IA)

  • There are greater than 300,000 invasive aspergillosis cases every year globally,17 and mortality rates as high as 70% have been reported18
  • Common symptoms include fever, especially recrudescent fever despite appropriate antibiotic treatment, chest pain and shortness of breath19
  • However, immunocompromised patients are those least likely to have overt symptoms, and progression of the disease is usually fast13
  • IA is associated with a reported case fatality rate of 58%, which varies considerably depending on the site of infection, and presence of underlying conditions.20 It can reach almost 100% if infection remains untreated in certain patient populations20,21

AmBisome® (liposomal amphotericin B) demonstrates in vitroa fungicidal activity against major Aspergillus species, including A. fumigatus and A. flavus.22

a. Caution must be taken when extrapolating in vitro data in the clinical setting.

Candida

Candida is a type of yeast that can become invasive and cause serious infections in internal organs (invasive candidiasis) and the bloodstream (candidaemia) in patients at risk, such as those in ICUs or those with a weakened immune system23
A common route of infection is through central venous catheters that are needed by patients in the ICUs for extended periods of time23
Candida species account for 70-90% of IFIs24
Candidaemia is one of the most common IFIs in immunocompromised ICU patients25
The most common Candida species that cause infections globally are C. albicans, Nakaseomyces glabratab, C. parapsilosis, C. tropicalis, and C. krusei,23,26-28; however, C. auris is an emerging, multi-drug resistant, fungal pathogen causing concern globally23,28,29 b. Formerly known as Candida glabrata
Candida is a type of yeast that can become invasive and cause serious infections in internal organs (invasive candidiasis) and the bloodstream (candidaemia) in patients at risk, such as those in ICUs or those with a weakened immune system23
A common route of infection is through central venous catheters that are needed by patients in the ICU for extended periods of time23
Candida species account for 70-90% of IFIs24
Candidaemia is one of the most common IFIs in immunocompromised ICU patients25
The most common Candida species that cause infections globally are C. albicans, Nakaseomyces glabratab, C. parapsilosis, C. tropicalis, and C. krusei,23,26-28; however, C. auris is an emerging, multi-drug resistant, fungal pathogen causing concern globally23,28,29 b. Formerly known as Candida glabrata

Invasive candidiasis (IC)

  • Common symptoms of invasive candidiasis include; a fever or chills that do not improve after antibiotic treatment23
  • There are an estimated 750,000 global cases of invasive candidiasis each year17
  • IC in ICUs is associated with a reported mortality rate of 40-55%30
  • In Europe, the day 30 mortality rates for candidaemia patients in ICUs, tertiary care, as well as general and teaching hospitals has been as high as 37-38%31

AmBisome® demonstrates in vitroa fungicidal activityc against a multitude of Candida species, including C. albicans, N. glabratab, C. krusei, C. parapsilosis, and C. tropicalis32

a. Caution must be taken when extrapolating in vitro data in the clinical setting. b. Formerly known as Candida glabrata. c. The majority of clinically important fungal species seem to be susceptible to amphotericin B, although intrinsic resistance has rarely been reported, for example, for some strains of S. schenckii, N. glabratab, C.krusei, C. tropicalis, C. lusitaniae, C. parapsilosis and A. terreus.

Mucormycetes

Mucormycetes is a genus of mould fungi that can cause a serious, but rare, fungal infection (mucormycosis) in at-risk patients23
These environmental fungi live in soil and decaying organic matter,23 and can cause rhinocerebral, pulmonary, gastrointestinal, cutaneous or disseminated infection in predisposed individuals33
The most common species are Rhizopus species and Mucor species34
Mucormycetes is a genus of mould fungi that can cause a serious, but rare, fungal infection (mucormycosis) in at-risk patients23
These environmental fungi live in soil and decaying organic matter,23 and can cause rhinocerebral, pulmonary, gastrointestinal, cutaneous or disseminated infection in predisposed individuals33
The most common species are Rhizopus species and Mucor species34

Mucormycosis

  • Signs and symptoms depend on the location of the infection (sinus and brain, lungs, skin, gastrointestinal tract, or disseminated)35-37 but can include swelling, fever, black lesions, blisters or ulcers, coughing, abdominal pain, nausea, and gastrointestinal bleeding23
  • Mucormycosis affects 0.005 to 1.7 per million population globally38
  • The estimated prevalence of mucormycosis is 910,000 cases globally, with around 900,000 of these cases localised to India,39 and mortality rates are reported to be between 33-96%,34,40,41 and vary depending on underlying disease and time to diagnosis39,40
  • World Health Organisation (WHO) estimated 140 cases per million population in India in 2021 - 80 times higher than in other parts of the world38

AmBisome® is recommended by the ECMM/MSGERC as a treatment of choice for mucormycosis42

Cryptococcus

Cryptococcosis is an invasive fungal infection affecting immunocompromised patients, usually caused by Cryptococcus neoformans or Cryptococcus gattii43
These two species are commonly found in soil, decaying wood, tree hollows and bird droppings, and can cause infection through inhalation23,43
Cryptococcal meningitis, predominantly caused by Cryptococcus neoformans, affects people living with advanced HIV, and has an estimated 223,100 cases globally each year44
Symptoms of cryptococcosis depend on the location of the infection (lungs, brain, skin or other organs), but can include coughing, breathlessness, and fever when in the lungs23,45-51, and headache, fever, nausea and vomiting, light sensitivity and confusion when affecting the brain23
Cryptococcosis is an invasive fungal infection affecting immunocompromised patients, usually caused by Cryptococcus neoformans or Cryptococcus gattii43
These two species are commonly found in soil, decaying wood, tree hollows and bird droppings, and can cause infection through inhalation23,43
Cryptococcal meningitis, predominantly caused by Cryptococcus neoformans, affects people living with advanced HIV, and has an estimated 223,100 cases globally each year44
Symptoms of cryptococcosis depend on the location of the infection (lungs, brain, skin or other organs), but can include coughing, breathlessness, and fever when in the lungs23,45-51, and headache, fever, nausea and vomiting, light sensitivity and confusion when affecting the brain23

Cryptococcal meningitis (CM)

  • Is associated with high mortality rates and is detrimental to quality of life52,53
  • ~250,000 patients are affected by CM globally per year54
  • CM contributes to 10-20% of all HIV-related deaths worldwide7
  • Mortality rate of 100% if CM infection remains untreated54

AmBisome® demonstrates similar efficacy to amphotericin B deoxycholate with fewer adverse events, in people living with advanced HIV with acute cryptococcal meningitis.55

Antifungal resistance RISK FACTORS AND DIAGNOSIS

References

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UK-AMB-0695 | November 2023