WHO’s who of killer fungi

4 minute read

The World Health Organisation has released its first “most wanted” list of potentially deadly fungal pathogens.

The World Health Organisation has named Cryptococcus neoformans as the most dangerous fungi from a public health and research point of view, followed by Candida auris, Aspergillus fumigatus and Candida albicans.

The four fungitives (fungi fugitives) make up the “critical priority group” of fungal pathogens as determined by the WHO, which received input from more than 400 public health clinicians and medical mycology experts.

There are 15 other fungal pathogens which made the list, organised into “high priority” and “medium priority” groups.

As immunocompromised groups of patients expand globally – solid organ transplant recipients, chemotherapy patients, people undergoing invasive treatments – cases of invasive fungal disease are growing as well.

There’s also evidence to suggest global warming is allowing some pathogenic fungi to expand its geographic range.

With only four classes of antifungal medicines currently available, and several multi drug-resistant strains of fungi emerging, the WHO is arguing for fungal pathogens to receive more than the current 1.5% of infectious disease research funding globally.

“Consequently, the evidence base is weak, and most treatment guidelines are informed by limited evidence and expert opinion,” the organisation said in a statement.

Because so little is known about fungal infections in general, it tends to rank low in terms of clinical suspicion, leading to misdiagnosis or delayed treatment and poor patient outcomes.

Cryptococcus neoformans

C. neoformans, which holds the dubious glory of being named the number one most critical fungal pathogen to get under control, typically affects the lungs, central nervous system and blood.

For infected people, mortality ranges from 40% to 60%, with average hospital length of stay between 18 and 39 days.

Those that do survive may end up blind, require shunts or have acute renal impairment.

It’s most commonly seen in people with weakened immune system, including HIV patients, people on immunosuppressant medicine, autoimmune disease patients and people with decompensated cirrhosis of the liver.

There are prophylactic and pre-emptive therapies which can protect against infection, but no vaccine.

The top priority for C. neoformans, according to the WHO, is better surveillance to establish the disease burden overall, and more data on its antifungal susceptibility.

Candida auris

C. auris, one of the yeasts which produces invasive candidiasis, has what the WHO calls “high outbreak potential” and is already intrinsically resistant to most available antifungals.

Resistance rates to fluconazole are as high as 100%, while susceptibility to other azoles was variable; it’s also around 35% resistant to amphotericin B and up to 8% resistant to echinocandins.

Mortality ranges from 30% to 50% in infected individuals, most commonly cancer or transplant patients.

Unlike rates of C. neoformans, which are thought to have remained steady over the last decade, case rates of C. auris have been climbing, especially during the pandemic.

Aspergillus fumigatus

Azole-resistant invasive aspergillosis, which is just one of the conditions A. fumigatus is implicated in, has a mortality rate between 50% and 90%, with infected patients spending up to 532 days in hospital.

In terms of public health risk, it was ranked as the most dangerous fungal pathogen of all.

Luckily, it has relatively high preventability, with the WHO recommending antifungal prophylaxis for high-risk groups along with screening for azole resistance even in azole-naïve patients – especially people with cancer or cystic fibrosis.

The rising rates of azole-resistant A. fumigatus is credited to widespread use of azole fungicides in agriculture.

Candida albicans

C. albicans differs from the other fungal pathogens in its critical risk cohort in that it can be part of the healthy human microbiome.

Under certain circumstances, it can multiply in mucosae and produce diseases like oropharyngeal candidiasis, vulvovaginal candidiasis and cutaneous candidiasis.

Like C. auris, C. albicans can also produce invasive candidiasis infections in the blood, eyes, heart, central nervous system and internal organs.

Unlike C. auris, incidence rates are thought to have remained relatively stable over the past decade and antifungal resistance is relatively uncommon.

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