Combatting fungal pandemics
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Combatting fungal pandemics

5.4.4

Sub-Field

Combatting fungal pandemics

The major fungal pathogens include Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. These may cause direct or indirect harm. For example, the emerging fungal pathogen behind Candidozyma auris infection, first identified in 2009, is becoming a widespread hospital threat, with the number of infections growing by 59 per cent between 2019 and 2020, and by 95 per cent between 2021 and 2022.10 But even strains that do not harm humans directly may harm them indirectly: While Pseudogymnoascus destructans — which causes white-nose syndrome in bats — was thought to be primarily a threat to biodiversity,11 its downstream consequences for ecosystem stability have been linked to increased human infant illness and death. Aspergillus sydowii affects coral reefs but has also spread into hospitals, where it causes respiratory infections. It has also been (controversially) found to drive lung cancer progression.

Future Horizons:

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5-yearhorizon

New drugs are deployed

Results from phase III trials of novel anti-fungals yield new drugs to deploy in hospitals. Experimental and computer models help illuminate the mechanisms of how fungi invade, which provides targets for mitigation. Vaccination strategy and insights in bats that helped mitigate the damage of white-nose syndrome (including grooming spread) reduce the impact of the next pandemic. A new small-molecule drug is discovered. Passive surveillance technology allows monitoring of the next pandemic threat.

10-yearhorizon

Control and development of anti-fungals improves

New anti-fungals that do not interfere with clinical anti-fungals are developed for agriculture. A major pharmaceutical company starts human trials with newly discovered natural products. Active surveillance technology prevents fungal pathogens emerging. Vaccines are developed against major fungal threats.

25-yearhorizon

Real-time pandemic prediction and control becomes possible

Predictive biology combines mechanistic models, ecological insights, surveillance and in vivo data on pathogenesis into real-time pandemic prediction and control.

Mitigation strategies include vaccines and RNA interference (via extracellular vesicles as a promising route),12 new small-molecule drugs and natural compounds that are isolated from bacteria and other sources where anti-fungal strategies have evolved. There is a need to replace broad-spectrum agricultural fungicides that poison the entire kingdom, moving towards a more tailored approach involving targeted fungicides that leave soil-fungal communities intact, lock down carbon and do not cause resistance in clinical anti-fungals. Research into these tailored approaches is ongoing but not yet mature.

More positively, two novel small-molecule anti-fungals — olorofim and fosmanogepix — are now in phase III trials.13 New synthetic chemicals are also being developed, as well as new approaches for delivering them. Manipulating the fungal microbiome or virome may guide their behaviour into being more favourable for us.

Combatting fungal pandemics - Anticipation Scores

The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate:

  1. The uncertainty related to future science breakthroughs in the field
  2. The transformative effect anticipated breakthroughs may have on research and society
  3. The scope for action in the present in relation to anticipated breakthroughs.

This chart represents a summary of their responses to each of these elements, which when combined, provide the Anticipation Potential for the topic. See methodology for more information.

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