What are invasive fungal infections?

Invasive fungal infections occur when fungi breach the body's defences and infect deep tissues — lungs, brain, blood, heart and other organs. Unlike superficial fungal infections (athlete's foot, oral thrush), invasive fungal infections are life-threatening and predominantly affect immunocompromised patients. The most important invasive fungi: Aspergillus fumigatus (mould — airborne spores, lungs); Candida species (yeast — bloodstream, ICU); Cryptococcus neoformans (yeast — HIV patients, meninges); Mucorales (mould — diabetes, lung/sinus); and the emerging superbug Candida auris.

Why are fungal infections so neglected?

Invasive fungal infections kill an estimated 3.75 million people per year — comparable to tuberculosis — yet receive approximately 1% of global infectious disease research funding. Reasons for neglect: most deaths occur in immunocompromised patients (HIV, cancer) who die of multiple causes, masking the fungal contribution; fungi are poorly recognised by clinicians; diagnostic tests are expensive and unavailable in LMICs; antifungal drugs (amphotericin B, azoles, echinocandins) are expensive and have access barriers; there are no vaccines for fungal infections; and pharmaceutical companies see limited commercial incentive. The 2022 WHO Fungal Priority Pathogen List is the first major attempt to correct this neglect.

What is Candida auris and why is it so concerning?

Candida auris is an emerging multidrug-resistant yeast — first identified in a Japanese patient's ear in 2009 and now present on every inhabited continent. It causes candidaemia (bloodstream infection) and wound infections in hospital patients. Concerning features: approximately 90% resistance to fluconazole (the most widely used antifungal); increasing resistance to echinocandins (second-line) and amphotericin B; difficult to identify (misidentified as other Candida by many lab systems — requires MALDI-TOF mass spectrometry or molecular testing); persistent environmental contamination of hospital surfaces (survives disinfection with many standard agents); and high mortality (approximately 30-60%).

How is invasive aspergillosis diagnosed and treated?

Diagnosis: CT chest (halo sign early — haemorrhagic infarct around fungal mass; air crescent sign late); serum/BAL galactomannan ELISA (sensitivity approximately 70-80% in haematological malignancy); beta-D-glucan; culture (positive in only approximately 50% — insensitive); PCR increasingly used. Treatment: voriconazole (first-line — landmark NEJM 2002 trial) significantly superior to amphotericin B; isavuconazole (alternative, fewer side effects — approval 2015); liposomal amphotericin B (for voriconazole-intolerant or suspected azole-resistant Aspergillus). Antifungal combination therapy is not routinely recommended.

What is the COVID-19 connection to fungal infections?

COVID-19 dramatically increased awareness of fungal infections as secondary complications: COVID-19 associated pulmonary aspergillosis (CAPA) — invasive aspergillosis complicating severe COVID-19, especially in ICU patients on corticosteroids; COVID-19 associated mucormycosis (CAM) — a devastating epidemic in India 2021 with approximately 47,000 cases, primarily diabetics receiving dexamethasone for COVID-19. Corticosteroids (essential COVID-19 treatment) suppress immunity → facilitate fungal superinfection. COVID-19 also caused lymphopenia, increasing susceptibility.

How is cryptococcal meningitis managed?

WHO recommended induction treatment: amphotericin B deoxycholate (0.7-1mg/kg/day IV) + flucytosine (100mg/kg/day orally) for 14 days. This combination reduces mortality by approximately 40% vs amphotericin monotherapy. Fluconazole 800mg/day: alternative induction when amphotericin/flucytosine unavailable. Consolidation: fluconazole 400mg/day for 8 weeks → maintenance fluconazole 200mg/day (until CD4 >200 on ART). High intracranial pressure management: daily therapeutic LP (very important — ICP >25 cmH2O should be normalised daily).

What is the WHO Fungal Priority Pathogen List?

In October 2022, WHO published the first-ever Fungal Priority Pathogen List — categorising 19 fungi into critical, high and medium priority groups based on impact (global burden, mortality, morbidity), dissemination (geographic spread, zoonotic potential) and one health aspects, as well as drug resistance and unmet research needs. Critical priority: Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, Candida albicans. This list — modelled on the Bacterial Priority Pathogen List — aims to focus R&D investment, diagnostic development, antifungal access and clinical research.

How does GMJ News cover invasive fungal infections?

GMJ News covers WHO Fungal Priority Pathogen List 2022, Candida auris spread, cryptococcal meningitis treatment and access, COVID-associated fungal infections, antifungal access in LMICs and the neglected burden. Invasive fungal infections are relevant to Georgian hospital infection control and PHIG's antimicrobial stewardship programme.

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Invasive Fungal Infections

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

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WHO published its first-ever Fungal Priority Pathogen List in October 2022 — recognising invasive fungal infections as a critically neglected global health crisis causing an estimated 3.75 million deaths per year, with aspergillosis, candidiasis (including the emerging multidrug-resistant Candida auris), and cryptococcal meningitis (112,000 deaths/year in HIV patients) leading the burden (WHO 2022). Invasive fungal infections predominantly kill immunocompromised patients (HIV, cancer, transplant, ICU patients) and are severely under-recognised, under-diagnosed and under-resourced in LMICs where diagnostic capacity and essential antifungals (amphotericin B, azoles) are often unavailable.

Key messages

WHO Fungal Priority Pathogen List — 2022

WHO published its first Fungal Priority Pathogen List in October 2022 — recognising invasive fungal infections as a critically neglected global health crisis causing an estimated 3.75 million deaths/year. Four critical priority pathogens: Cryptococcus neoformans; Aspergillus fumigatus; Candida auris; Candida albicans.

3.75 million deaths/year — largely unrecognised

Invasive fungal infections kill approximately 3.75 million people per year — comparable to TB, yet receive a fraction of the research, funding and clinical attention. The burden falls overwhelmingly on immunocompromised patients (HIV, cancer, transplant, ICU).

Candida auris — the superbug

Candida auris is a multidrug-resistant emerging yeast — causing hospital outbreaks on every inhabited continent, with up to 90% resistance to fluconazole and increasing resistance to echinocandins and amphotericin B. Difficult to detect and decontaminate.

Cryptococcal meningitis kills 112,000/year

Cryptococcus neoformans causes meningitis in HIV patients with CD4 <100 cells/μL — killing approximately 112,000 people/year. Amphotericin B + flucytosine induction is the WHO-recommended regimen; widespread access barriers exist in LMICs.

Aspergillosis — 300K+ invasive cases/year

Invasive aspergillosis — caused by Aspergillus fumigatus — affects immunocompromised patients (haematological malignancies, transplant, corticosteroids, COVID-19), causing 30-50% mortality despite voriconazole treatment.

Diagnosis is the biggest gap

The primary barrier to managing fungal infections is misdiagnosis or delayed diagnosis — most LMICs lack fungal culture capacity, beta-D-glucan/galactomannan testing and Cryptococcus antigen testing. Invasive aspergillosis and candidiasis are frequently diagnosed at autopsy.

Key statistics

3.75M

estimated deaths/year from invasive fungal infections

WHO 2022

~112K

deaths/year from cryptococcal meningitis

WHO

300K+

invasive aspergillosis cases/year

GAFFI/WHO

Oct 2022

WHO first Fungal Priority Pathogen List published

WHO

90%

fluconazole resistance in Candida auris (most strains)

CDC/WHO

global health R&D budget targeting fungi (vs ~13% for bacteria)

GAFFI

Estimated global deaths from priority fungal pathogens — WHO 2022

Source: WHO Fungal Priority Pathogen List 2022. Cryptococcus and Aspergillus cause the most deaths.

Glossary of key terms

Invasive aspergillosis (IA)
WHO/ESCMIDInfection of lungs (and dissemination) by Aspergillus fumigatus in immunocompromised hosts. Presenting as new pulmonary infiltrates, halo sign on CT (early — haemorrhagic infarct around fungal hyphae). Treated with voriconazole (first-line); isavuconazole; liposomal amphotericin B. Serum/BAL galactomannan ELISA is a key diagnostic biomarker.

Cryptococcal meningitis
WHOCaused by Cryptococcus neoformans (predominantly) or C. gattii — in HIV patients with CD4 <100 and other severely immunocompromised patients. Presents with headache, fever, altered mental status. High opening pressure on LP (may require repeated LP for pressure management). Treated with amphotericin B + flucytosine induction → fluconazole consolidation/maintenance.

Candida auris
WHO/CDCAn emerging multidrug-resistant Candida species — first identified in 2009 in Japan. Causes healthcare-associated candidaemia; colonises skin/environmental surfaces persistently; difficult to identify (misidentified as other Candida by standard lab methods without MALDI-TOF or molecular testing). Up to 90% resistant to fluconazole; increasing echinocandin resistance.

Mucormycosis
WHORapidly progressive, life-threatening mould infection — caused by Mucor, Rhizopus and related fungi. Predominantly affects diabetics (especially DKA) and immunocompromised patients. Rhino-orbito-cerebral, pulmonary or cutaneous forms. India COVID-19 associated mucormycosis (2021): approximately 47,000 cases after dexamethasone use in diabetics — a dramatic illustration of immune suppression triggering fungal infection.

Beta-D-glucan (BDG)
ESCMID/IDSAA cell wall component of most fungi — measurable as a serum biomarker for invasive fungal infection. Not specific (also elevated by contamination, certain antibiotics). Used as a screening test for invasive candidiasis and PCP in high-risk patients. Not elevated in Cryptococcus or Mucor.

Flucytosine (5-FC)
WHO EMLAn antifungal — essential combination partner for amphotericin B in cryptococcal meningitis induction (superior to amphotericin B alone). Prevents relapse and improves survival. However, flucytosine is unavailable in most African countries — a critical access gap. WHO and MSF advocate strongly for flucytosine availability.